KR20080112290A - Method for preparing optically active chromium oxide compound - Google Patents

Abstract

It is an object of the present invention to provide an efficient method for producing an optically active chromium oxide compound, which is an important intermediate of the benzopyran compound, which is effective for the treatment of arrhythmia, and as a solution thereof, optically active titanium represented by formulas (1), (2), and the like. Using the complex as a catalyst,

(Tue 1)

 Provided is a method for preparing an optically active chromium oxide compound by subsidiary oxidation of the optically active chromium compound with high enantioselectivity and high chemical yield.

(Tue 2)

Description

Process for producing optically active chromene oxide compound

The present invention relates to a method for the efficient preparation of an optically active chromium oxide compound which is an important intermediate of the benzopyran compound effective for the treatment of arrhythmias.

Benzopyran compounds useful as antiarrhythmic drugs and methods for their preparation are disclosed. That is, a benzopyran compound is prepared by subsidiary epoxidation of a chromium compound with an optically active manganese complex to give an optically active chromium oxide compound, and then ring-opening an epoxy with an amine compound (see Patent Document 1).

A method for producing an optically active chromium oxide compound by subsidiary epoxidation of a chromium compound with an optically active manganese complex has already been disclosed (Patent Document 2, Patent Document 3, Patent Document 4, Patent Document 5 and Patent Document 6). Reference). The said patent document describes the manufacture example of the optically active chromium oxide compound which uses an optically active manganese complex as a catalyst, and uses iodine benzene, sodium hypochlorite, or 30% hydrogen peroxide as a co-oxidant.

In the subsidiary oxidation reaction by the optically active manganese complex, an additive such as 4-phenylpyridine-N-oxide called an axial ligand in addition to the co-oxidant is required, and an optically active chromium oxide compound by another method that does not use an axial ligand. The manufacturing method of is desired.

On the other hand, by using an asymmetric optically active manganese complex, a method capable of producing an optically active chromium oxide compound with a high chemical yield and an optical yield even in an amount of 0.01 to 0.2 mol% has been described (Patent Document 7 As the co-oxidant, only an example using iodine benzene has been described, and therefore an industrially advantageous and efficient production method has been desired.

Regarding the optically active titanium complex, the di-μ-oxo titanium sararen complex uses hydrogen peroxide as an oxidizing agent, and the reaction proceeds with high enantio selectivity in the subsidiary epoxidation reaction of various simple olefins having no hetero atom. Has been reported. However, there have been no reports of olefin compounds having a hetero atom and chromene compounds (Non-Patent Document 8).

(Patent Document 1) Japanese Unexamined Patent Application Publication No. 2001-151767

(Patent Document 2) Japanese Unexamined Patent Application Publication No. 05-301878

(Patent Document 3) Japanese Unexamined Patent Application Publication No. 07-285983

(Patent Document 4) Japanese Unexamined Patent Application Publication No. 08-245668

(Patent Document 5) WO2005 / 090357A1

(Patent Document 6) WO2005 / 080368A2

(Patent Document 7) Japanese Unexamined Patent Application Publication No. 11-335384

(Non-Patent Document 8) K. Matsumoto, Y. Sawada, B. Saito, K. Sakai, T. Katsuki, Angew. Chem. Int. Ed. (2005), 44, 4935-4939.

(Problem that invention tries to solve)

Provided are methods for preparing optically active chromium oxide compounds, which are important intermediates of the benzopyran compounds effective for the treatment of arrhythmias.

(Means to solve the task)

The present invention has been conducted by the present inventors as a result of earnestly studying a method for producing an optically active chromium oxide compound, which is an important intermediate of a benzopyran compound effective for the treatment of arrhythmias, by using an optically active titanium complex as a catalyst. With the thio selectivity and high chemical yield, it has been found that an optically active chromenoxide compound can be prepared and the present invention has been completed.

The present invention provides the first aspect of the formula (1), formula (1 '), formula (2), formula (2'), formula (3), formula (3 '), formula (4) and formula (4').

(Tue 1)

R ¹ in (Equation (1), formula (1 ') and Expression (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4') is a hydrogen atom, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy groups, C _{6 - 12} aryloxy or C _{6 -22} aryl group (the aryl group, C _{1 - 4} alkyl group (said alkyl group, halogen atom optionally may be substituted), C _{1 -.. 7} is an alkoxy group, or a benzyloxy group which optionally may be substituted, optically active or optically inactive denotes a),

R ² is a hydrogen atom, a halogen atom, a C _{1 - 18} represents an aryl, _{- 4} alkyl, C _{1 - 4} alkoxy groups, C _{6 - 12} aryloxy or C ₆

R ³ is C _{1 - 4} alkyl group, C _{6 - 18} is an aryl group, or, one or two R ³ the case of forming the ring, represents a divalent group _of C _{3 -5,}

R ⁴ are each independently a hydrogen atom, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a denotes a nitro group or a cyano group,

M is in the TiJ ¹ J ² (TiJ ¹ J ^2, Ti denotes a titanium atom, J ¹ and J ² are, each independently, a halogen atom, C _{1 - 4} represent or an alkoxide, the J ¹ and J ² One to represent an oxygen atom, or J ¹ and J ² together to form a ring, where a divalent group is the formula (5)

(Tue 2)

(In formula, O represents an oxygen atom, O is represented by following formula (6) as O-E-O in Formula (1), and is represented as O-E-O in Formula (1 '). In formula (2), it is represented by following formula (7) as O-E-O in formula (2), In formula (2 '), it is represented by following formula (7') as O-E-O, In 3), O-E-O is represented by the following formula (8), and in formula (3 '), it is represented by the following formula (8') as O-E-O, and in formula (4), the following is represented by O-E-O. It is represented by Formula (9), and is represented by following formula (9 ') as O-E-O in (4'),

(Tue 3)

b is an integer of ^1-10 , and R <^1> , R <^2> , R <^3> and R <^4> are the same as the above. ), Formula (11), formula (12), or formula (13)

(Tue 4)

(Formula (10) in R ^5, R ^6, R ⁷ and R ⁸ are, each independently, a hydrogen atom, a cyano group, a nitro group, a halogen atom, a C _{1 -4} alkyl group (said alkyl group, a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, C _{1 -4} alkoxycarbonyl group (the alkoxy group, an alkylcarbonyloxy group, an alkyl carbonyl . a carbonyl group and alkoxycarbonyl group may be arbitrarily substituted with halogen atom) it may also optionally be substituted with a), C _{1 -4} alkoxy group (the alkoxy group, a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 - 4} alkoxy group, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, C _{1 -4} ah alkoxycarbonyl group (the alkoxy group, alkylcarbonyloxy group, alkylcarbonyl group and alkoxycarbonyl group, It may be optionally substituted with a halogen atom. .) May also optionally be substituted), C _{1 -4} alkyl-carbonyl group (the alkylcarbonyl group is a halogen atom, C _{6 -10} aryl group (the C _{6 - 10} aryl group is a halogen atom, a hydroxy group, a cyano group , nitro, C _{1 - 4} alkyl, or C _{1 -. 4} may be an optionally substituted alkoxy group), may also optionally be substituted with a), C _{1 -. 4} alkyl-carbonyl (N-C _{1 - 4} alkyl) amino group (the alkylcarbonyl (N- alkyl) amino group which may be optionally substituted with a halogen atom.), C _{1 -4} alkoxycarbonyl group (the alkoxy group, there may be optionally substituted with a halogen atom.), C _{6 - 10} aryl carbonyl group (the arylcarbonyl group is a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} may be a substituted alkoxy group, a cyano group or a nitro group.), C _{6 - 10} aryl-carbonyl (N-C _{1 - 4} alkyl) amino group (the arylcarbonyl (N- alkyl) Mino group, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or a nitro group may be substituted), benzyl carbonyl group, a formyl group, a carbamoyl group, C _{1 -. 4} alkylsulfonyl group , C _{6 -10} aryl sulfonyl group (wherein group alkylsulfonyl and arylsulfonyl, a halogen atom, C _{1 - 4} alkyl, C _{1 -. 4} group may be substituted alkoxy group, a cyano group or a nitro group), a sulfamoyl group , C _{1 - 4} alkyl sulfonamide group, a C _{6 -10} aryl sulfonamide group (said alkyl group is a sulfonamide group and an aryl sulfonamide, halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or a nitro group group may be substituted), a bead (C _1-4 alkyl sulfone) already deugi (the beads (alkyl sulfone) alkyl sulfone of deugi already has, a halogen atom, C _{1 -. 4} alkyl, C _{1 - 4} alkoxy group, a cyano It may be substituted with a no group or a nitro group.), A beads (C _6-10 aryl sulfone) imide group (the Beads (aryl sulfone) aryl sulfone of the imide group is a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or a nitro group may be substituted), [N, N '- . (C 1 - ₄ alkyl sulfone) (C _{6 - 10} aryl sulfone) already deugi (a [N, N '- (alkyl sulfone) (aryl sulfone) already in deugi alkyl sulfone and aryl sulfone, a halogen atom, C _{1 - 4} alkyl , C _{1 - 4} alkoxy group, a cyano group or represents a nitro group may be substituted).

₆ is an alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) _- (10) of the R ⁹ and R ¹⁰ are, each independently represent a hydrogen atom, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _1. or may be by a hydroxy group optionally substituted), C _{6 -14} aryl group (the aryl group, a halogen atom, a hydroxy group, a nitro group, a cyano group, C _{1 -6} alkyl group (said alkyl group, a halogen atom, a C _{1 - 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) or by a hydroxy group optionally may be substituted) or C _{1 -.. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) optionally substituted by May be substituted.)

(11) and (12) of the R ₉ and R ¹⁰ are, each independently represent a hydrogen atom, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 -6} optionally substituted alkoxy group (the alkoxy group is a halogen atom may be.), or by a hydroxy group optionally may be substituted.) or a C _{6 -14} aryl group (the aryl group, a halogen atom, a hydroxy group, a nitro group, a cyano group, C _{1 -6} alkyl group (said alkyl group, a halogen atoms, C _{1 -6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) or may be optionally substituted by a hydroxy group) or C _{1 -. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom May be optionally substituted by.),

The partial ring structure A in formulas (11) and (12) is a 5-, 6- or 7-membered ring that forms a condensed ring with the benzene ring moiety (both R ¹¹ (R ¹¹ is a halogen atom, a hydroxy group, a C _{1 -6} alkyl group (said alkyl group, a halogen atom, a hydroxy group, a cyano group, an amino group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, or C _{1 -4} alkoxycarbonyl group (the alkoxy group, the alkylcarbonyloxy may be substituted with a halogen atom group, alkylcarbonyl group and an alkoxycarbonyl group.) may also optionally be substituted.), C _{1 - 6} alkoxy group (the alkoxy group, a halogen atom, a hydroxy group, a cyano group, an amino group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkyl-carbonyl group, or C _{1 -4} alkoxycarbonyl group (the alkoxy group, Al The alkylcarbonyloxy group, the alkylcarbonylamino group and the alkoxycarbonyl group may be optionally substituted with a halogen atom.)

Optionally may be substituted), a nitro group, a cyano group, a formyl group, a formamide group, a carbamoyl group, sulfo group, sulfonyl group, sulfamoyl group, sulfonyl group, amino group, carboxyl group, C ₁ to _{- 6} alkylamino group, di-C _{1 - 6} alkylamino group, C _{1 - 6} alkylcarbonyl group, C _{1 - 6} alkyl sulfonamide group, C _{6 - 14} aryl sulfonamide group, C _{1 - 6} alkylaminocarbonyl group, di C _{1 - 6} alkylamino a carbonyl group, C _{1 - 6} alkylcarbonyl group, C _{1 -6} alkoxycarbonyl groups, C _{1 - 6} alkylsulfonyl, C _{6 -14} aryl sulfonyl group, or C _{6 -14} aryl group (the alkylamino group, dialkylamino group, alkyl carbonyl The carbonylamino group, alkylsulfonamide group, arylsulfonamide group, alkylaminocarbonyl group, dialkylaminocarbonyl group, alkylcarbonyl group, alkoxycarbonyl group, alkylsulfonyl group, arylsulfonyl group and arylcarbonyl group are optionally substituted with halogen atoms. It may be exchanged.)

H is an integer of 1 to 6, and when h is 2 to 6, R ₁₁ may be the same or different), and may be optionally substituted with 1 to 3 oxygen atoms and nitrogen as constituent atoms of the ring. Atoms or sulfur atoms may be included alone or in combination. The number of unsaturated bonds in the ring is 1, 2 or 3, including the unsaturated bonds of the condensed benzene ring, and the carbon atoms constituting the ring are carbonyl. Or thiocarbonyl)).

X in the formula (13), NR ²⁰ represents the (R ^20, means a hydrogen atom or a C _{1 -4} alkyl group),

Y in Formula (13) represents a bond, SO or SO ₂ ,

Z is C _{1 -4} alkyl group (said alkyl group, with 1 to 5 halogen atoms or a phenyl group (the phenyl group, C ₁ in the formula (13) _- may also optionally be substituted by ₄ alkyl) may also optionally be substituted by .) or a phenyl group (the phenyl group, C _{1 -} represents an optionally can also be substituted with _four alkyl groups).

₆ alkoxy group (said alkoxy, _- formula (13) in W is a hydrogen atom, a hydroxy group, C ₁ May be optionally substituted with a halogen atom), halogen atom, C _{1 -. 4} alkyl or C _{1 - 6} alkyl sulfonamide group (wherein the alkyl group and alkyl sulfone amide group, represents a may be optionally substituted with a halogen atom).

Expression (13) in the R ⁹ and R ¹⁰ are, each independently represent a hydrogen atom, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 -6} alkoxy group (said alkoxy group may be arbitrarily substituted with a halogen atom.) Or optionally substituted by a hydroxyl group.)

Or C _{6 -14} aryl group (the aryl group, a halogen atom, a hydroxy group, a nitro group, a cyano group, C _{1 - 6} alkyl group (said alkyl group, a halogen atom, a C _{1 - 6} alkoxy group (said alkoxy group is optionally substituted with a halogen atom there may be), or by a hydroxy group optionally may be substituted) or C _{1 -.} a ₆ alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) may also optionally be substituted by a) it shows a)... The chromium compound to be shown is epoxidized by an oxidizing agent in a solvent, wherein formula (14), formula (15), formula (16) or formula (17)

(Tue 5)

(Wherein R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , A, W, X, Y and Z are the same as above. The absolute arrangement of carbon atoms represented by * is (R) or ( A method for producing an optically active chromium oxide compound represented by S).

As a second viewpoint, the formula (1), formula (1 '), formula (2), formula (2'), formula (3), formula (3 '), formula (4) and formula (4') Using an optically active titanium complex represented by either formula as a catalyst,

The formula (10) in R ₅ and R ₆ are, each independently, a hydrogen atom, a cyano group, a nitro group, a halogen atom, a C _{1 -4} alkyl group (said alkyl group, a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, C _1-4 alkoxycarbonyl group (the alkoxy group, alkylcarbonyloxy group, alkylcarbonyl group and an alkoxycarbonyl group ., there may be arbitrarily substituted with halogen atom) it may also optionally be substituted with a), C _{1 -4} alkoxy group (the alkoxy group, a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, C _1-4 alkoxycarbonyl group (the alkoxy group, alkylcarbonyloxy group, alkylcarbonyl group and an alkoxycarbonyl group, the halogen atom may be substituted with optionally Im a May be substituted.) To,

C _{1 - 4} alkylcarbonyl group (the alkylcarbonyl amino group may be arbitrarily substituted with halogen atom), C _{1 - 4} alkyl-carbonyl (N-C _{1 - 4} alkyl) amino group (wherein the alkyl-carbonyl (N - alkyl) amino group, and may be arbitrarily substituted with halogen atom), C _{6 -10} aryl-carbonyl (N-C _1-4 alkyl) amino group (the arylcarbonyl (N- alkyl) amino] group, a halogen atom, C _1-4 alkyl group, C _{1 -. 4} alkoxy group, a cyano group or may be substituted with a nitro group), a carbamoyl group, a bead (C _1-4 alkyl sulfone) already deugi (the beads (alkyl sulfone) already alkyl deugi sulfone, a halogen atom, C _{1 - 4} alkyl, C _{1 -. 4} may also be substituted with an alkoxy group, a cyano group or a nitro group), a bead (C _6-10 aryl sulfone) imide group (the beads (aryl sulfone) already aryl sulfone of deugi is a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or a nitro group Substitution may be) or [N, N. '- ( C 1 - 4 alkyl sulfone) (C _{6 - 10} aryl sulfone) imide group (the [N, N' - (alkyl sulfone) (aryl sulfone) already alkyl sulfone and aryl sulfone of deugi is a halogen atom, C _{1 - 4} alkyl, C _{1 -. 4} alkoxy group, a cyano group or may be substituted with a nitro group) represents,

(10) of the R ⁷ is a hydrogen atom, a cyano group, a nitro group, a bead (C _{1 - 4} alkyl sulfone) already alkyl sulfone of deugi already deugi (the beads (alkyl sulfone) is a halogen atom, C _{1 - 4} alkyl group, C _{1 -4} may be substituted with an alkoxy group, a cyano group or a nitro group.), beads (C _{6 -10} aryl sulfone) imide group (the beads (aryl sulfone) is an aryl sulfone of the imide group, halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or may be substituted by nitro) or [N, N '-. ( C 1 - 4 alkyl sulfone) (C _{6 - 10} aryl sulfone) imide group (the [N, N '- (alkyl sulfone) (aryl sulfone) already alkyl sulfone and aryl sulfone of deugi is a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} may be a substituted alkoxy group, a cyano group group or nitro .)

Formula (10) in R ⁸ is a hydrogen atom, a nitro group or a C _{1 - 4} alkyl

(The alkyl group may be optionally substituted with a halogen atom.),

(10) of the R ⁹ and R ¹⁰ is, C _{1 - 6} alkyl

(The alkyl group may be optionally substituted with a halogen atom.)

A method of producing the optically active chromium oxide compound according to the first aspect, wherein the chromium compound represented by the formula (10) represented by the above is substituted with an oxidizing agent as a solvent.

As a 3rd viewpoint, R <^5> and R <^6> in said Formula (10) respectively independently represents a hydrogen atom, a nitro group, a fluorine atom, a methoxy group, a methylcarbonylamino group, or a methylcarbonyl (N-ethyl) amino group. , formula (10) is of R ^7, a hydrogen atom, a nitro group or beads (C _{1 -4} alkyl sulfone) imide] a group, the formula (10) is of R ^8, a hydrogen atom, a nitro group or a trifluoromethyl The manufacturing method of the optically active chromium oxide compound as described in the 2nd viewpoint which represents a methyl group and R <^9> and R <^10> in Formula (10) show a methyl group,

As a fourth point of view, the formula (1), formula (1 '), formula (2), formula (2'), formula (3), formula (3 '), formula (4) and formula (4') Using the optically active titanium complex represented by any one as a catalyst, the partial ring structure of A in Formula (11) or Formula (12) is formula (a), formula (b), formula (c), formula (d), Expression (e), Expression (f), Expression (g), Expression (h), Expression (i), Expression (j), Expression (k), Expression (l), Expression (m), Expression (n), Expression (o), Expression (p), Expression (q), Expression (r), Expression (s), Expression (t), Expression (u), Expression (ｖ), Expression (w), Expression (x), In formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae), formula (af), formula (ag) and formula (ah) It is displayed by either

(Tue 6)

(Formula (a), formula (b), formula (e), formula (f), formula (g), formula (h), formula (i), formula (j), formula (k), formula (l) ), Formula (m), formula (n), formula (p), formula (q), formula (ｖ), formula (w), formula (x), formula (ab), formula (ae), formula (af ) and formula (ag) is in the R ¹² and R ¹³ are, each independently, a hydrogen atom, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 -6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom .), an amino group, a hydroxy group, C _{6 - 14} aryl group, an aryl group with C _{2 -9} hetel (said aryl and heteroaryl groups all q of R ¹⁸ (R ¹⁸ represents the same meaning as R ^11, q is 1, for 2-3 represent an integer, q is 2 or 3, R ¹⁸ may be the same or different) may also optionally be substituted with a), C _{1 -. 6} alkylaminocarbonyl group, di C _{1 - 6} alkylamino a carbonyl group, C _{1- 6} alkylcarbonyloxy group, C _{1 -6} alkylcarbonyl group (the alkylcarbonyloxy group and the alkylcarbonyl group is a halogen atom Optionally may be substituted), C _{1 -. 6} alkyl-carbonyl group, C _{3 -8} cycloalkyl group, a C _{1 - 6} alkoxycarbonyl, C _{1 -6} alkyl sulfonyl group (said cycloalkyl group, an alkoxycarbonyl group and an alkyl alcohol sulfonyl group may be arbitrarily substituted with halogen atom), a carboxyl group, C _{6 -. 14} aryl group (the aryl group may be arbitrarily substituted with halogen atom).

Or C _{2 -9} may be optionally substituted with a heteroaryl group), C _{6 -. 14} aryl, C _2-9 heteroaryl group (wherein the aryl and heteroaryl groups all q of R ¹⁸ (R ¹⁸ is R ¹¹ . represents the same meanings, q is an integer of 1-3, in the case of q is 2 or 3, the R ¹⁸ may be the same or different) may also optionally be substituted with a), C _{1 -. 6} alkyl amino group, a di-C _{1 -6} alkylamino group, a C _{1 - 6} alkylcarbonyl group, C _{3 - 8} cycloalkyl group, a C _{1 - 6} alkoxycarbonyl group, C _{1 - 6} alkylsulfonyl, C _{6 - 14} arylsulfonyl group, C _2-9 heteroaryl sulfonyl group (the aryl sulfonyl and heteroaryl-sulfonyl group all q of R ¹⁸ (R ¹⁸ represents the same meaning as R ^11, q is an integer of 1 ~ 3, q is 2 or 3 in the case, R ¹⁸ may be the same or different.) may also optionally be substituted with a), Reubok group, C _{6 -14} aryl group or a C _{2 -9} heteroaryl group (the aryl group and heteroaryl group are all q of R ¹⁸ (R ¹⁸ represents the same meaning as R ^11, q is an integer from 1 to 3 When q is 2 or 3, R ¹⁸ may be the same or different), and may be optionally substituted by

Formula (a), Formula (b), Formula (c), Formula (d), Formula (f), Formula (g), Formula (h), Formula (j), Formula (k), Formula (m) , Formula (n), formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (ｖ), formula (w) R ¹⁴ , R ¹⁵ , R ^{16 in} formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae) and formula (af) R ¹⁷ each independently represent a hydrogen atom, a halogen atom, a C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 -. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), amino group, hydroxy group, C _{6 -. 14} aryl group, C _{2 -9} heteroaryl group (the aryl group and heteroaryl group all of r r ¹⁹ (r ¹⁹ represents the same meaning as r ^11, r has the same meaning as q) by optionally may be substituted), C _{1 -6} alkylamino group, a di-C _{1 -6} alkylamino group, C _{1 -. 6} alkylcarbonyloxy group, C _{1 -6} alkylcarbonyl group (the alkylcarbonyloxy group and an alkyl Carbonyl Group may be arbitrarily substituted with halogen atom), C _{1 -6} alkylcarbonyl group, C _{3 -. 8} cycloalkyl group, a C _{1 - 6} alkoxycarbonyl, C _{1 -6} alkyl sulfonyl group (said cycloalkyl group, an alkoxycarbonyl group and the alkylsulfonyl group may be arbitrarily substituted with halogen atom), a carboxyl group, C _{6 -14} aryl group (the aryl group may be arbitrarily substituted with halogen atom) or a C _{2 -.. 9} heteroaryl group optionally may be substituted by there), C _{3 -8} cycloalkyl _groups-can be optionally substituted with (said cycloalkyl group is a halogen atom, C _{1 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), amino group or hydroxy group). C _{1 -6} alkoxy group (said alkoxy group, a halogen atom, C _{1 - 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom .), A carboxyl group, an amino group, a hydroxy group, C _{6 - 14} aryl group or C _{2 -9} heteroaryl group (the aryl group and heteroaryl group all of r R ¹⁹ (R ¹⁹ represents the same meaning as R ^11, r is .. represents the same meaning as q) may also optionally be substituted by a) may also optionally be substituted with a), C _{1 -6} alkoxy group (said alkoxy group, a halogen atom, C _{1 -. 6} alkoxy group ( the alkoxy group may be arbitrarily substituted with halogen atom), a carboxyl group, a hydroxy group, C _{6 -. 14} aryl group or C _{2 - 9} heteroaryl group (wherein the aryl and heteroaryl groups all r of r ¹⁹ (r ¹⁹ is r ¹¹ .. represents the same meanings, r represents the same meaning as q) may also optionally be substituted by a) may also optionally be substituted by a) hydroxyl group, C _{6 -. 14} aryl group, C _{2 -9} heteroaryl (The aryl group and hetero aryl group Two r of R ¹⁹ (. R ¹⁹ represents the same meaning as R ^11, r has the same meaning as q) may also optionally be substituted with a), C _{1 -. 6} alkylcarbonyloxy group, a nitro group, a cyano group, a formyl group, forms an amide group, an amino group, a sulfo, C _{1 - 6} alkylamino group, a di-C _{1 - 6} alkylamino group, C _{6 - 14} aryl group, a C _{2 -9} heteroaryl group (the aryl group and heteroaryl arylamino group are all r of r ¹⁹ (. r ¹⁹ represents the same meaning as r ^11, r has the same meaning as q) may also optionally be substituted with a), C _{1 -. 6} alkyl-carbonyl group, C _{1- 6} alkyl sulfonamide group, a carbamoyl group, C _{1 - 6} alkylaminocarbonyl group, di C _{1 - 6} alkylaminocarbonyl group, C _{1 - 6} alkylcarbonyl group, C _{6 - 14} aryl group, a C _{2 -9} heteroaryl group (The arylcarbonyl group and heteroarylcarbonyl Both r of R ¹⁹ (. R ¹⁹ represents the same meaning as R ^11, r has the same meaning as q) it may also optionally be substituted with a), C _{1 -. 6} alkoxycarbonyl group, a sulfamoyl group, C _{1 - 6} alkylsulfonyl, C _{6 - 14} arylsulfonyl group, C _2-9 heteroaryl sulfonyl group (the aryl sulfonyl and heteroaryl-sulfonyl group of all r r ¹⁹ (r ¹⁹ represents the same meaning as r ¹¹ .., r have the same meanings as q) may also optionally be substituted with a) carboxyl group or a C _{2 -9} heterocyclic methacrylic group (wherein the heterocyclyl rilneun, a halogen atom, C _{1 - 6} alkyl group (the alkyl group, a halogen atom, C _{1 - 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), may be optionally substituted with amino group, carboxyl group or hydroxy group), C _{1 -.} arbitrarily ₆ alkoxy group (the alkoxy group is a halogen atom May be substituted C.), C _{6 - 9} heteroaryl group (wherein the aryl and heteroaryl groups all r of R ¹⁹ (R ¹⁹ represents the same meaning as R ^11, r is q, and the same meaning _{- 14} aryl group, C ₂ are shown) may also optionally be substituted with a), a hydroxy group, a nitro group, a cyano group, a formyl group, forms an amide group, an amino group, a C _{1 -. 6} alkyl group, a di-C _{1 - 6} alkylamino group, C _{1 - 6} alkyl a carbonyl group, C _{1 - 6} alkyl sulfonamide group, a carbamoyl group, C _{1 - 6} alkylaminocarbonyl group, di C _{1 - 6} alkylaminocarbonyl group, C _{1 - 6} alkylcarbonyl group, C _{1 - 6} alkoxycarbonyl group, a sulfamoyl group, C _{1 -} denoted by ₁₄ aryl may be optionally substituted with a carbonyl group), _{- 6} alkylsulfonyl group, a carboxyl group or a C _6.

Q in said Formula (c), Formula (d), Formula (p), Formula (q), Formula (iii), Formula (w), Formula (ab), Formula (ac), and Formula (ad) is O (Oxygen atom), S (sulfur atom), SO (sulfinyl group) or SO ₂ (sulfonyl group).) The chromene compound represented by the formula (11) or formula (12) is a subsidiary agent in the solvent as an oxidant. Method for producing an optically active chromium oxide compound according to the first aspect characterized by epoxidation,

As a 5th viewpoint, the manufacturing method of the optically active chromium oxide compound of the 4th viewpoint whose R <^9> and R <^10> in said Formula (11) or Formula (12) is a methyl group,

As a 6th viewpoint, A in said Formula (11) or Formula (12) is following Formula (a), Formula (b), Formula (i), Formula (k), Formula (o), Formula (p), Expression (s), Expression (y), Expression (y), Expression (ae), Expression (ag) or Expression (ah)

(Tue 7)

A method for producing an optically active chromium oxide compound according to the fourth or fifth viewpoint represented by (wherein R ¹² , R ^{13 ,} R ¹⁴ , R ¹⁵ and R ¹⁶ are the same as the fourth viewpoint),

As a 7th viewpoint, A in Formula (11) or Formula (12) is said Formula (a), Formula (b), Formula (i), Formula (k), Formula (o), Formula (p), Formula (s), formula (i), formula (y), formula (ae), formula (ag) or formula (ah), formula (a), formula (b), formula (i), formula (k), R ¹² in formula (p), formula (ae), formula (ae) and formula (ag) And R ¹³ is each independently a hydrogen atom, C _{1 -6} alkyl group (said alkyl group is a halogen atom, C _{1 -. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), optionally substituted with an amino group or a hydroxyl group And formula (a), formula (b), formula (k), formula (o), formula (p), formula (s), formula (i), formula (y) and formula ( ae) of R ^14, R ¹⁵ and R ¹⁶ are, each independently represent a hydrogen atom, a halogen atom or a C _{1 -6} alkyl group (said alkyl group, a halogen atom, a C ₁₆ alkoxy group (said alkoxy group is optionally substituted with a halogen atom may be), an amino group, a hydroxy group, C _{1 -. 6} alkylaminocarbonyl group, di C _{1 - 6} alkylaminocarbonyl group, C _{1 - 6} alkylcarbonyloxy group, C _{1 -6} alkylcarbonyl group (the alkylcarbonyloxy group and alkyl group may be arbitrarily substituted with halogen atom), C _{1 -. 6} alkyl-carbonyl group, C _{3 -8} when Claw-alkyl group or a C _{1 -. 6} alkoxy may be optionally substituted with a carbonyl group) to indicate, Q is O (process for producing an optically active chromene oxide compounds described in the sixth aspect that represents an oxygen atom),

As an eighth viewpoint, A in said Formula (11) or Formula (12) is Formula (a), Formula (b), Formula (i), Formula (k), Formula (o), Formula (p), Formula (s), formula (i), formula (y), formula (ae), formula (ag) or formula (ah), formula (a), formula (b), formula (i), formula (k), R <^12> and R <^13> in Formula (p), Formula (ae), Formula (ae), and Formula (ag) are a hydrogen atom and a methyl group, Formula (a), Formula (b), Formula (k), Formula (o) ), a group of the formula (p), type (s), type (v), formula (y) and equation (ae) of the R ^14, R ¹⁵ and R ¹⁶ are each independently a hydrogen atom, a halogen atom, or C _{1 - 6} alkyl group (said alkyl group, a halogen atom, C _{1 -. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), amino group, hydroxy group, C _{1 - 6} alkylaminocarbonyl group, di C _{1 - 6} alkylaminocarbonyl group , C _{1 - 6} alkylcarbonyloxy group, C _{1 -6} alkylcarbonyl group (the alkylcarbonyloxy group and the alkylcarbonyl group may be optionally substituted with a halogen atom.), C _{1 - 6} alkylcarbonyl group, C _{3 - 8} Cycloalkyl group or a C _{1 -. 6} alkoxy may be optionally substituted with a carbonyl group) to indicate, Q is O (process for producing an optically active chromene oxide compounds described in the seventh aspect that represents an oxygen atom),

As a ninth point of view, the formula (1), formula (1 '), formula (2), formula (2'), formula (3), formula (3 '), formula (4) and formula (4') Using the optically active titanium complex represented by either formula as a catalyst, the chromene compound represented by the formula (13) in which both R ⁹ and R ¹⁰ in the formula (13) represents a methyl group is used as the oxidizing agent in the solvent. A method for producing the optically active chromium oxide compound according to the first aspect, characterized in that the subsidiary epoxidation,

As a tenth aspect, i) the method for producing an optically active chromium oxide compound according to the ninth aspect, wherein W in the formula (13) represents a hydrogen atom, a hydroxyl group, a methoxy group, a chlorine atom, a bromine atom, a methyl group, an ethyl group, or a methanesulfonamide group ,

Claim 11 as a point of view, the formula (13), with the in Y SO ₂ (sulfonyl group), Z is C _{1 - 4} represent an alkyl group, a ninth aspect or the tenth method of manufacturing an optically active chromene oxide compounds described in perspective,

Claim 12 as a point of view, the formula (13), and Y is a bond in, Z is C _{1 -} optically active as described in the tenth aspect that indicates _four groups chromene oxide compound production method of,

As a 13th viewpoint, in said Formula (1), Formula (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4), and Formula (4') the R ^1, C _{6 - 22} aryl group (the aryl group, C _{1 -. 4} alkyl group (said alkyl group may be arbitrarily substituted with halogen atom) C _{1 -7} alkoxy groups, or benzyloxy, and optionally may be substituted , Optically active or optically inactive).

R ² is a hydrogen atom, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy groups, C _{6 - 12} aryloxy group or a C _{6 - 18} represents an aryl group,

R ³ is C _{1 - 4} alkyl group, C _{6 - 18} is an aryl group, or, one or two R ³ the case of forming the ring, represents a divalent group of C _{3 -5,}

R ⁴ are each independently a hydrogen atom, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a denotes a nitro group or a cyano group,

M is, TiJ ¹ J ² (for TiJ ¹ J ^2, Ti is a titanium atom, J ¹ and J ² are, each independently, a halogen atom, C _{1 - 4} represent or an alkoxide, the J ¹ and J ² It becomes one and represents an oxygen atom, or J <^1> and J <^2> become one, it forms a ring, and the said Formula (5) which is a bivalent group (partial structure O-E-O in formula, O is an oxygen atom. In formula (1), it is represented by said formula (6) as O-E-O, In formula (1 '), it is represented by said formula (6') as O-E-O, In formula (2), it is O- It is represented by said formula (7) as E-O, is represented by said formula (7 ') as O-E-O in formula (2'), and is represented by said formula (8) as O-E-O in formula (3). Is represented by the formula (8 ') as O-E-O in formula (3'), is represented by the formula (9) as O-E-O in formula (4), and formula (4). Iv) is represented by the above formula (9 ') as O-E-O, b is an integer of 1 to 10, and R ¹ , R ² , R ³ And R ⁴ is as described above.) A method for producing the optically active chromium oxide compound according to the first aspect, wherein

As a 14th viewpoint, in said Formula (1), Formula (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4), and Formula (4') the R ^1, a phenyl group (the phenyl group, C _{1 -. 4} alkyl group (said alkyl group may be arbitrarily substituted with halogen atom), a benzyloxy group, or a C _{1 -.} may be optionally substituted with a _7-alkoxy), or naphthyl group (the naphthyl group, C _{1 -4} alkyl group (said alkyl group may be arbitrarily substituted with halogen atom), C _{1 -.. 7} may be optionally substituted with an alkoxy group, or a phenyl group) represents a,

R ² represents a hydrogen atom,

R ³ represents a C _{3 -5} divalent group in which two R ³ are one to form a ring,

R ⁴ represents a hydrogen atom,

M is, TiJ ¹ J ² (for TiJ ¹ J ^2, Ti is a titanium atom, J ¹ and J ² are, each independently, a halogen atom, C _{1 -4} alkoxy, or represent a DE, the J ¹ and J ² It becomes one, represents an oxygen atom, or J <^1> and J <^2> become one, and form a ring, and the said Formula (5) which is a bivalent group (partial structure O-E-O in a formula, O is an oxygen atom) In formula (1), it is represented by said formula (6) as O-E-O, In formula (1 '), it is represented by said formula (6') as O-E-O, In formula (2), it is O- It is represented by said formula (7) as E-O, is represented by said formula (7 ') as O-E-O in formula (2'), is represented by said formula (8 ') as HO-E-O, In formula (4), it is represented by said formula (9) as O-E-O, In formula (4 '), it is represented by said formula (9') as O-E-O, and b is an integer of 1-10. ^{, R 1, R 2, R} 3 and R ⁴ is optically active as described in the thirteenth aspect that represents the same as above) shows a.) chroman Process for producing a compound oxide,

As a 15th viewpoint, the usage-amount of an optically active titanium complex is 0.001-100 mol% with respect to the chromium compound represented by Formula (10), Formula (11), Formula (12), or Formula (13)- The manufacturing method of the optically active chromium oxide compound in any one of 14th viewpoint,

As a sixteenth aspect, the solvent used in the subsidiary epoxidation reaction is a halogen solvent, an aromatic hydrocarbon solvent, an ester solvent, an ether solvent, a nitrile solvent, an alcohol solvent, or a mixture of the solvents. A method for producing an optically active chromium oxide compound according to any one of Claims 14 to 14,

As the 17th point of view, the oxidizing agent used in the subtitle epoxidation reaction is iodide benzene, sodium hypochlorite, m-chloroperbenzoic acid, orson (DuPont®), hydrogen peroxide, urea-hydrogen peroxide adduct (UHP), oxadi The optically active chromate according to any one of the first to the fourteenth viewpoints of lidine, N-methylmorpholine oxide (NMO), t-butylhydropearloxide (TBHP), cumene hydropearloxide (CHP) or a mixture of these oxidizing agents. Process for preparing men oxide compound,

As an eighteenth aspect, the method for producing the optically active chromium oxide compound according to the seventeenth aspect, wherein the oxidant used in the subtitle epoxidation reaction is hydrogen peroxide water, urea-hydrogen peroxide adduct (UHP), or a mixture of these oxidants,

As a 19th viewpoint, the manufacturing method of the optically active chromium oxide compound as described in the 18th viewpoint whose oxidizing agent used for a subsidiary epoxidation reaction is hydrogen peroxide and whose density | concentration is 1-100 mass%,

As a 20th viewpoint, the usage-amount of the oxidizing agent used for a subsidiary epoxidation reaction is 1-10 equivalent with respect to the chromate compound represented by said Formula (10), Formula (11), Formula (12), or Formula (13). The manufacturing method of the optically active chromium oxide compound in any one of 1st viewpoint-14th viewpoint,

As a 21st viewpoint, the addition method of the oxidizing agent used for a subsidiary epoxidation reaction is a manufacturing method of the optically active chromium oxide compound as described in the 20th viewpoint which is partial addition or continuous addition,

As a 22nd viewpoint, the addition method of the oxidizing agent used for a subsidiary epoxidation reaction is continuous addition, The manufacturing method of the optically active chromium oxide compound as described in 21st viewpoint whose addition rate is 0.01-40000 equivalent every hour,

As a twenty third aspect, the method for producing an optically active chromium oxide compound according to the twenty-first aspect, wherein the addition method of the oxidant used in the subsidiary epoxidation reaction is divided addition and the number of division is in the range of 2 to 100;

As a 24th viewpoint, the manufacturing method of the optically active chromium oxide compound as described in any one of a 1st viewpoint thru | or a 23rd viewpoint whose reaction temperature of a subsidiary epoxidation reaction is from 0 degreeC to the reflux temperature of the solvent used,

As a 25th viewpoint, the manufacturing method of the optically active chromium oxide compound as described in any one of a 1st viewpoint thru | or a 24th viewpoint whose range of the pressure in the reaction system of a subsidiary epoxidation reaction is 10 kPa-1100 kPa,

(Effects of the Invention)

According to the present invention, an optically active chromium oxide compound which is an important intermediate of a useful benzopyran compound effective for the treatment of arrhythmias can be efficiently produced.

(The best mode for carrying out the invention)

In this specification, "n" is normal, "i" iso, "s" is secondary, "t" is tertiary, "c" is cyclo, "o" is ortho, and "m" is In meta, "p" means para.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail. In the present invention, the titanium complex used as a catalyst for epoxidizing the chromate compound with an oxidizing agent is formula (1), formula (1 ′), formula (2), formula (2 ′), formula (3), formula ( 3 '), equation (4) and equation (4)

(Tue 8)

R ¹ in (Equation (1), formula (1 ') and Expression (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4') has,

A hydrogen atom, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy groups, C _{6 - 12} aryloxy or C _{6- 22} aryl group (the aryl group, C _{1 - 4} alkyl group (said alkyl group, a halogen atom optionally may be substituted.), or, C _{1 -7} May be optionally substituted with an alkoxy group or benzyloxy group and is optically active or optically inactive.),

R ² is a hydrogen atom, a halogen atom, a C _{1 - 18} represents an aryl, _{- 4} alkyl, C _{1 - 4} alkoxy groups, C _{6 - 12} aryloxy or C ₆

R ³ is C _{1 - 4} alkyl group, C _{6 - 18} aryl group, or, if the two R ³ is one to form a ring represents a divalent group of C _{3 -5,}

R ⁴ are each independently a hydrogen atom, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a denotes a nitro group or a cyano group,

M is TiJ ¹ J ² (In TiJ ¹ J ² , Ti is a titanium atom, and J ¹ And J ² are, each independently, a halogen atom, C _{1 -} to form a ring is a _4-alkoxy represent a DE, or the J ¹ and J ² is the one shown an oxygen atom, or, one J ¹ and J ² Formula (5)

(Tue 9)

(In formula, O represents an oxygen atom, O is represented by following formula (6) as O-E-O in Formula (1), and is represented as O-E-O in Formula (1 '). In formula (2 '), it is represented by following formula (7) as O-E-O in formula (2), In formula (2'), it is represented by following formula (7 ') as O-E-O, In 3), O-E-O is represented by the following formula (8), and in formula (3 '), it is represented by the following formula (8') as O-E-O, and in formula (4), the following is represented by O-E-O. It is represented by Formula (9), and is represented by following formula (9 ') as O-E-O in (4'),

(Tue 10)

b is an integer of ^1-10 , and R <^1> , R <^2> , R <^3> and R <^4> are as above.

Each substituent in said Formula (1), Formula (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4), and Formula (4') is demonstrated. do.

R ¹ in the formula (1) and (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4') is a hydrogen atom, a halogen atom, C _{1 - 4} alkyl, C _{1 -} optionally ₄ alkyl group (said alkyl group, a halogen atom _{- 4} alkoxy groups, C _{6 - 12} aryloxy group or a C _{6 - 22} aryl group (the aryl group, C ₁ may be substituted), or, C _{1 -.. 7} is an alkoxy group, or a benzyloxy group which optionally may be substituted, optically active or optically inactive shows a).

Formula (1) and (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4') specifically describe in R ¹ do.

As said halogen atom, a fluorine atom, a chlorine atom, a bromine atom, and an oxo atom are mentioned,

The C _{1 - 4} As the alkyl group, there may be mentioned methyl, ethyl, n- propyl, i- propyl, n- butyl, i- butyl, s- butyl group and t- butyl group,

The C _{1 - 4} alkoxy group includes a methoxy group, an ethoxy group, n- propoxy, i- propoxy, c- propoxy, n- butoxy, i- butoxy, s- butoxy group, t- Butoxy group, c-butoxy group, etc. are mentioned,

The C _{6 - 12} aryl-oxy group, aryloxy group include phenyl, 1-naphthyloxy group, 2-naphthyloxy group, 2-penny rilok time, such as 3-penny rilok time and 4-time penny rilok There is,

The C _{6 - 22} aryl group (the aryl group, C _{1 - 4} alkyl group (said alkyl group may be arbitrarily substituted with halogen atom), C _{1 -. 7,} and an alkoxy group, or a benzyloxy group optionally may be substituted, an optical Active or optically inert),

Phenyl group, 2-methylphenyl group, 2-trifluoromethylphenyl group, 4-methylphenyl group, 2-ethylphenyl group, 2-pentafluoroethylphenyl group, 3, 5- dimethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group , 4-methoxyphenyl group, 2-ethoxyphenyl group, 2-i-propoxyphenyl group, 2-benzyl oxyphenyl group, 3,5-dimethoxyphenyl group, 1-naphthyl group, 2-naphthyl group, 2-biphenylyl group , 3-biphenylyl group, 4-biphenylyl group, 2-methyl- 1-naphthyl group, 2-phenyl- 1-naphthyl group, 2-methoxy- 1-naphthyl group, 2- [3, 5- dimethylphenyl ] -1-naphthyl group, 2- [4-methylphenyl] -1-naphthyl group, 2- (o-biphenylyl) -1-naphthyl group, 2- (m-biphenylyl) -1-naphthyl group, and 2- (p-biphenylyl) -1-naphthyl group etc. are mentioned. In addition, the C _{6- 22} aryl group may be optically active or optically inactive.

R ¹ in the formula (1) and (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4') is a hydrogen Atom, fluorine atom, chlorine atom, bromine atom, oxo atom, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group, methoxy group , Ethoxy group, n-propoxy group, i-propoxy group, c-propoxy group, n-butoxy group, i-butoxy group, s-butoxy group, t-butoxy group, c-butoxy group, phenyloxy group , 1-naphthyloxy group, 2-naphthyloxy group, phenyl group, 2-methylphenyl group, 2-trifluoromethylphenyl group, 4-methylphenyl group, 2-ethylphenyl group, 3, 5- dimethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 2-ethoxyphenyl group, 2-i-propoxyphenyl group, 2-benzyloxyphenyl group, 3, 5-dimethoxyphenyl group, 1-naphthyl group, 2-naphthyl group, 2-biphenylyl group, 3-biphenylyl group, 4-biphenylyl group, 2-phenyl-1- naphthyl group, 2-meth When 1-naphthyl group, 2- (m- biphenylyl) -1-naphthyl group, 2- (p- biphenylyl) -1-naphthyl group are preferred, and

Moreover, in these, as R <^1> , a phenyl group, 2-methylphenyl group, 2-trifluoromethyl phenyl group, 2-ethylphenyl group, 2-methoxyphenyl group, 2-benzyloxyphenyl group, 1-naphthyl group, 2-naphthyl group, 2 -Biphenylyl group, 2-phenyl-naphthyl group, 2-methoxy- 1-naphthyl group, 2- (m-biphenylyl)-1-naphthyl group, 2- (p-biphenylyl) -1 -Naphthyl group (the said 2-phenyl- 1-naphthyl group, 2-methoxy- 1-naphthyl group, 2- (m-biphenylyl)-1-naphthyl group, or 2- (p-biphenylyl)- 1-naphthyl group is optically active or optically inactive.),

Among these, as R ¹ , a phenyl group, 2-methylphenyl group, 2-trifluoromethylphenyl group, 2-methoxyphenyl group, 2-benzyloxyphenyl group, and 2-phenyl-1-naphthyl group are more preferable.

The formula (1) and (1 '), Formula (2), Formula (2' R ² in), Formula (3), Formula (3 '), Formula (4) and (4') is a hydrogen atom, a halogen atom, a C _{1 - 4} alkyl group, _C-4 alkoxy group, C _{6 - 18} represents an _aryl-12 aryloxy or C _6.

The formula (1), the formula (1 ') and Expression (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4') a R ² specifically in the Explain.

As said halogen atom, a fluorine atom, a chlorine atom, a bromine atom, and an oxo atom are mentioned,

As said C _{- 4} alkyl group, a methyl group, an ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group, etc. are mentioned,

As said C _{- 4} alkoxy group, a methoxy group, an ethoxy group, n-propoxy group, i-propoxy group, c-propoxy group, n-butoxy group, i-butoxy group, s-butoxy group, t-butok And a c-butoxy group,

As the C _{6 -12} aryloxy group, an oxy group include phenyl, 1-naphthyloxy group, 2-naphthyloxy group, 2-penny rilok time, such as 3-penny rilok time and 4-time penny rilok There is,

The C _{6 - 18} aryl group includes a phenyl group, a 3, 5-dimethylphenyl group, 4-methylphenyl, 1-naphthyl, 2-naphthyl group, 2-penny group, 2-phenyl-1-naphthyl group, 2- Methyl-naphthyl group, 2- [3, 5- dimethyl phenyl] -1-naphthyl group, 2- [4-methylphenyl] -1-naphthyl group, 2-methoxy-naphthyl group, etc. are mentioned. have.

The formula (1) and (1 '), Formula (2), Formula (2' R ² in), Formula (3), Formula (3 '), Formula (4) and (4') is a hydrogen Atom, fluorine atom, chlorine atom, bromine atom, oxo atom, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, t-butyl group, methoxy group, phenyloxy group, 1-naphthyloxy group , 2-naphthyloxy group, phenyl group, 3, 5- dimethylphenyl group, 4-methylphenyl group, 3, 5-dimethoxyphenyl group, 4-methoxyphenyl group, 1-naphthyl group, 2-naphthyl group, 2-biphenylyl group , 3-biphenylyl group, 4-biphenylyl group, 2-methoxy-1-naphthyl group are preferable,

Among these, as R ² , a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an oxo atom, a methyl group, an ethyl group, n-propyl group, i-propyl group, n-butyl group, t-butyl group, methoxy group, Phenyl oxy group, a phenyl group, 1-naphthyl group, 2-naphthyl group, 2-biphenylyl group is more preferable,

Moreover, in these, as R <^2> , a hydrogen atom is further more preferable.

R ³ in the formula (1) and (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4') are, C _{- 4} alkyl group, C _{6 -18} aryl group, or, if the two R ³ is one to form a ring represents a divalent group of C _{3 -5.}

The formula (1), the formula (1 ') and Expression (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4' specifically the R ³ in) Explain.

As said C _{- 4} alkyl, a methyl group, an ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group, etc. are mentioned,

The C _{6 - 18} aryl group, a phenyl group, a 3, 5-dimethylphenyl group, 2, 4, 6-trimethyl-phenyl, 4-methylphenyl group, a 1-naphthyl group, 2-penny group, 2-phenyl-1-naphthyl Tyl group, 2-methyl-1- naphthyl group, 2- [3, 5- dimethylphenyl] -1-naphthyl group, 2- [4-methylphenyl] -1-naphthyl group, 2-methoxy-1-naphthyl group, etc. Can be

When 2 to form a ring is that one of R ³ is a group 2 of C _{3 -5-valent,} and the like can be a trimethylene group and a tetramethylene group.

The formula R ³ in (1) and (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4') is a phenyl group, The tetramethylene group which the 3, 5- dimethylphenyl group, 2, 4, 6-trimethylphenyl group, 4-methylphenyl group, and two R <^3> couple | bonded is preferable,

Further, it is more preferably a tetra-2 of R ³ are bonded to each other as methylene R ³ from the aforementioned.

R ⁴ in the formula (1) and (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4') is a hydrogen An atom, a halogen atom, a C _{- 4} alkyl group, a C _{- 4} alkoxy group, a nitro group, or a cyano group is represented.

The formula (1), the formula (1 ') and Expression (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4') a R ⁴ particularly in Explain.

As said halogen group, a fluorine atom, a chlorine atom, a bromine atom, and an oxo atom are mentioned,

As said C _{- 4} alkyl group, a methyl group, an ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group, etc. are mentioned,

As said C _{- 4} alkoxy group, a methoxy group, an ethoxy group, n-propoxy group, i-propoxy group, n-butoxy group, i-butoxy group, s-butoxy group, t-butoxy group, etc. are mentioned. .

R ⁴ in the formula (1) and (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4') is a hydrogen Atom, fluorine atom, chlorine atom, bromine atom, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group, methoxy group, ethoxy group , n-propoxy group, i-propoxy group, n-butoxy group, i-butoxy group, s-butoxy group, t-butoxy group are preferable,

Among these, as R ⁴ , a hydrogen atom is more preferable.

M in the above formula (1) and (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4') has, TiJ ¹ J ²

(In TiJ ¹ J ² , Ti is a titanium atom, J ¹ and J ² each independently represent a halogen atom, C _{- 4} alkoxide, or J ¹ and J ² become one to represent an oxygen atom. Or, J ¹ and J ² are combined to form a ring, and the formula (5) is a divalent group.

(Tue 11)

(In formula, O represents an oxygen atom, O is represented by following formula (6) as O-E-O in Formula (1), and is represented as O-E-O in Formula (1 '). In formula (2 '), it is represented by following formula (7) as O-E-O in formula (2), In formula (2'), it is represented by following formula (7 ') as O-E-O, In 3), O-E-O is represented by the following formula (8), and in formula (3 '), it is represented by the following formula (8') as O-E-O, and in formula (4), the following is represented by O-E-O. It is represented by Formula (9), and is represented by following formula (9 ') as O-E-O in (4'),

(Tue 12)

b is an integer of ^1-10 , and R <^1> , R <^2> , R <^3> and R <^4> are the same as the above.

In addition, when J <^1> and J <^2> become one, and represent an oxygen atom, Formula (1), Formula (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 ') (4) and (4 ') are mononuclear oxo titanium complexes as structures of the entire molecule, and when J ¹ and J ² become one to form a ring to represent formula (5), which is a divalent group, Formula (1), Formula (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and Formula (4') are the structures of the entire molecule. It becomes the micro-oxo titanium (b + 1) nuclear complex which is a complex.

Moreover, Formula (1), Formula (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and Formula (4') are the said oxo titanium complexes. Or, in the case of the μ-oxo titanium (b + 1) nuclear complex, the optically active titanium complex of the present invention is a mixture of these oxo titanium complexes or the μ-oxo titanium (b + 1) nuclear complex in which b is any one of 1-10. It may be.

As preferable J <^1> and J <^2> , the case where J <^1> and J <^2> come together and represents an oxygen atom, or J <^1> and J <^2> become one, forms a ring, and represents Formula (5) which is a bivalent group is mentioned. In these cases, the optically active titanium complex is a mononuclear oxo titanium complex or a μ-oxo titanium (b + 1) nuclear complex (b is an integer of 1 to 10).

Moreover, about the optically active titanium complex of this invention, the optically active titanium sallan complex or Formula (2) represented by said Formula (1), Formula (1 '), Formula (3'), and Formula (3 '), Formula ( 2v), it divides according to the type of the titanium sallan complex represented by Formula (4) and Formula (4 '), and demonstrates formation of a preferable substituent and the structure of the whole molecule | numerator.

In the optically active titanium salylene complex represented by the formula (1), formula (1 ′), formula (3) and formula (3 ′), J ¹ and J ² become one to form a ring, and the aforementioned bivalent group It is represented by Formula (5), and it is preferable that b is 1 in Formula (5). In this case, the formula (1), formula (1 ′), formula (3), and formula (3 ′) represent a mu-oxo titanium dinuclear complex represented by the following formulas (18) and (18 ′) as the structure of the entire molecule. Becomes

(Tue 13)

(In formula, O-NH-N-O is represented by following formula (19) in formula (1), formula (19 ') in formula (1'), and formula (20) and formula (2) in formula (2). 2 ＇) in equation (20＇)

(Tue 14)

(In formula, R <^1> , R <^2> , R <^3> and R <^4> are the same as the above.)

And the complex represented by the formula (18 ′) is a current isomer of the complex represented by the formula (18).)

Particularly preferable combinations of substituents and the structure of the entire molecule of the optically active titanium salane complex will be described. Especially preferable optically active titanium salylene complex is represented by Formula (18) and Formula (18 '), and partial structure O-NH-N-O is a following formula (21), (21'), (22) Or equation (22)

(Tue 15)

And (aRSΔ, aRSΔ) -di μ-oxo titanium dinuclear complexes and (aSRΛ, aSRΛ) -di-μ-oxo titanium dinuclear complexes.

As combination of especially preferable substituent in the optically active titanium sallan complex represented by said Formula (2), Formula (2 '), Formula (4) and Formula (4'), following formula (23), (23 '), (24) and (24 ms)

(Tue 16)

(Wherein M represents TiJ ¹ J ² , J ¹ and J ² become one to represent an oxygen atom, or form one to form a ring to represent the formula (5) above, which is a divalent group) In b, b represents an integer of 1 to 10, and the partial structure O-E-O is represented by the following formulas (25), (25 '), (26) or (26') respectively.

(Tue 14)

The mononuclear oxo titanium complex or micro-oxo titanium (b + 1) body (b is an integer of 1-10) represented by these is mentioned.

Next, optically active titanium represented by Formula (1), Formula (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and Formula (4'). The manufacturing method of a complex is demonstrated.

Formula (29), Formula (29 '), Formula (31) or Formula (31') which is the ligand of the titanium sallan complex represented by Formula (2), Formula (2 '), Formula (4) and Formula (4'). With respect to the sallan ligand represented by), the salen compound represented by the following formula (28), formula (28 '), formula (30) or formula (30') can be reduced and produced, respectively.

Examples of the reducing agent include sodium borohydride (NaBH ₄ ), sodium cyanide borohydride (NaBH ₃ CN), lithium aluminum hydride (LiAlH ₄ ), and the like, and sodium borohydride (NaBH ₄ ) is preferable.

(Tue 18)

The optically active titanium salane complexes represented by the formulas (2), (2 ′), (4) and (4 ′) include the corresponding alkane ligands as titanium alkoxides, titanium tetrachlorides or titanium tetrabromide and dichloromethane. After reacting in an organic solvent such as water, water or a hydrous solvent (a mixed solvent in which water is contained in an organic solvent at a mass% of 0.1 to 100%), and examples of the organic solvent to be used include THF, methanol, and i-propanol. It can be prepared by treating with). The amount of water used is preferably in the range of 1 to 1000 moles, more preferably in the range of 1 to 10 moles, based on the equivalent of the sallan ligand.

In addition, in the reaction system, the optically active titanium salane complex may be produced, and the subtitle epoxidation reaction of the chromate compound may be performed without isolation as a catalyst.

At this time, the addition of water can also be performed by adding hydrogen peroxide water used as the oxidizing agent. As a titanium compound, titanium alkoxide is preferable, and as said titanium alkoxide, titanium tetramethoxide, titanium tetraethoxide, titanium tetra n-propoxide, titanium tetra i-propoxide, titanium tetra n-butoxide, and Titanium tetra t-butoxide, etc. are mentioned, Among these, titanium tetra i-propoxide [Ti (Oi-Pr) ₄ ] is more preferable. The amount of the titanium alkoxide to be used is preferably in the range of 1 to 2 moles with respect to 1 mole of the salan ligand.

The optically active titanium salylene complexes represented by the formulas (1), (1 ′), (3) and (3 ′) are described in Non-patent Document 8 (Angew. Chem. Int. Ed. (2005), 44, 4935-4939.) It can manufacture according to the method of description. That is, the corresponding salen ligand is reacted with titanium alkoxide, and a titanium complex is formed while reducing one of two imino bonds of the salen ligand by a Meerwein-Ponndrof-Verley (MPV) reduction reaction. It can be produced by treating with water or a water-containing solvent (a mixed solvent in which water is contained in an organic solvent in a mass% of 0.1 to 100%, and organic solvents used include THF, methanol, and i-propanol). .

In addition, in the reaction system, the optically active titanium salylene complex may be produced, and a subsidiary epoxidation reaction of the chromate compound may be performed without isolation as a catalyst.

Moreover, as said titanium alkoxide, titanium tetramethoxide, titanium tetraethoxide, titanium tetra n-propoxide, titanium tetra i propoxide, titanium tetra n-butoxide, titanium tetra t-butoxide, etc. are mentioned. Among these, titanium tetra i-propoxide Ti (Oi-Pr) ₄ ] is preferable. As for the usage-amount of titanium alkoxide, the range of 1-2 mol is preferable with respect to 1 mol of said salen ligands. Moreover, the range of 1-1000 mol is preferable with respect to the equivalent of said salen ligand, and, as for the usage-amount of water, the range of 1-10 mol is more preferable.

The reaction solvent at the time of producing an optically active titanium complex is a non-flotonic organic solvent, a flotonic organic solvent, or a mixture of these solvents. Examples of the non-flotone organic solvents include halogen solvents, aromatic hydrocarbon solvents, ester solvents, ether solvents, and nitrile solvents. Specific examples thereof include dichloromethane, chloroform, 1,2-dichloroethane, Chlorobenzene, toluene, ethyl acetate, tetrahydrofuran, diethyl ether, butyronitrile, propionitrile, acetonitrile and the like. Alcohol solvents are mentioned as a flotonic organic solvent, Specifically, ethanol, i-propanol, t-butanol, etc. are mentioned.

Preferred reaction solvents are dichloromethane, 1,2-dichloroethane, chlorobenzene, toluene and ethyl acetate, which are non-flotone organic solvents.

In the manufacturing method of this invention, Formula (1), Formula (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4), and Formula (4') By carrying out the subsidiary epoxidation of the chromate compound which is a starting raw material using the optically active titanium complex represented by the above, one of the curable isomers of a chromate oxide compound can be manufactured with a high selectivity. Specifically, by using any one of the complex of Formula (1) or the complex of Formula (1 '), one of the bicyclic isomers of an optically active chromium oxide compound can be selectively produced. By using either the complex of Formula (2) or the complex of Formula (2 '), one of the bicyclic isomers of an optically active chromium oxide compound can be manufactured selectively. By using either the complex represented by Formula (3) or the complex of Formula (3 '), one of the bispherical isomers of an optically active chromium oxide compound can be manufactured selectively. By using either the complex represented by Formula (4) or the complex of Formula (4 '), the bispherical isomer of an optically active chromium oxide compound can be manufactured selectively.

Next, the manufacturing method of the optically active chromium oxide compound of this invention is demonstrated. Formula (10), Formula (11), Formula (12), or Formula (13).

(Tue 19)

(In formula (10), R <^5> , R < ⁶ >, R <7> and R < ⁸ >,

Each independently represent a hydrogen atom, a cyano group, a nitro group, a halogen atom, a C _{1 -4} alkyl group (said alkyl group, a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 - 4} alkoxy, C _{1- 4} alkyl carboxylic carbonyloxy group, C _{1 - 4} alkyl optionally substituted with a carbonyl group, C _{1 -4} alkoxycarbonyl group (the alkoxy group, an alkylcarbonyloxy group, an alkyl-carbonyl group and alkoxycarbonyl group may be optionally substituted with a halogen atom.) may be substituted), C _{1 -4} alkoxy group (the alkoxy group, a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 -. 4} alkoxy, C _{1 -4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl amino group, C _{1 -4} alkoxycarbonyl group (the alkoxy group, the alkylcarbonyloxy may be substituted with a halogen atom group, alkylcarbonyl group and an alkoxycarbonyl group.) may also optionally be substituted.), C _{1 - 4} alkylcarbonyl group (the alkylcarbonyl group is a halogen atom, a phenyl group (said phenyl group is a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 -} may also optionally be substituted with a _4-alkoxy-4 alkyl, or C ₁ It may also optionally be substituted with a)), C _{1 -.. 4} alkyl-carbonyl (N-C _{1 - 4} alkyl) amino group (wherein the alkylcarbonyl (N- alkyl) amino group may be arbitrarily substituted with halogen atom). , C _{1 - 4} alkoxycarbonyl group (the alkoxy group, there may be arbitrarily substituted with halogen atom), C _{6 -10} aryl-carbonyl group (said aryl carbonyl amino group, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or a nitro group may be substituted), C _{6 -. 10} aryl-carbonyl (N-C _{1 - 4} alkyl) amino group (the arylcarbonyl (N- alkyl) amino group, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} Al May be substituted with a group, a cyano group or a nitro group), a benzyl carbonyl group, a formyl group, a carbamoyl group, C _{1 -. 4} alkylsulfonyl group, C _{6 -10} aryl sulfonyl group (wherein the alkylsulfonyl group and arylsulfonyl group, a halogen atom, C _{1 - 4} alkyl, C1 _{1- 4} alkoxy group, a cyano group or a nitro group may be substituted), sulfamoyl group, C _{1 -. 4} alkyl sulfonamide group, a C _{6 -10} aryl-sulfonamide group (group wherein the alkyl sulfone amide group, and aryl sulfonamide, halogen atom, C _{1 - 4} alkyl, C _{1 -. 4} alkoxy group, a cyano group or a nitro group may be substituted), a bead (C _{1 - 4} alkyl sulfone) already deugi (the beads (alkyl sulfone) alkyl sulfone of deugi already has, a halogen atom, C _{1 - 4} alkyl, C _{1 -. 4} may be substituted with an alkoxy group, a cyano group or a nitro group), a bead (C _6-10 Aryl sulfone) imide group (Aryl sulfone of the said beads (aryl sulfone) imide group is a halogen circle Here, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or may be substituted by nitro),. [N, N ' - (C 1 - 4 alkyl sulfone) (C _{6 - 10} aryl sulfone); an imide group (the [N, N '- (alkyl sulfone) (aryl sulfone) alkyl sulfone and aryl sulfone of the imide group is a halogen atom, C _{1 - 4} alkyl, C _{1- 4} alkoxy group substituted with a cyano group or a nitro group May be used.)

(10) of the R ⁹ and R ¹⁰ each independently represent a hydrogen atom, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 - 6} is an alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) or. there may be optionally substituted by a hydroxy group), C _{6 -14} aryl group (the aryl group, a halogen atom, a hydroxy group, a nitro group, a cyano group, C _{1 -6} alkyl group (said alkyl group, a halogen atom, a C _{1 - 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), or may be by a hydroxy group optionally substituted) or C _{1 -. 6} alkoxy group optionally substituted by (wherein the alkoxy group may be arbitrarily substituted with halogen atom). May be used.)

(11) and (12) of the R ⁹ and R ¹⁰ each independently represent a hydrogen atom, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 - 6} alkoxy group (said alkoxy group is optionally substituted with a halogen atom may be.), or by a hydroxy group optionally may be substituted.) or a C _{6 -14} aryl group (the aryl group, a halogen atom, a hydroxy group, a nitro group, a cyano group, C _{1 -6} alkyl group (said alkyl group, a halogen atom , C _{1 - 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) or by a hydroxy group optionally may be substituted) or C _{1 -. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom. May be optionally substituted).

(11) and (12) are all in the part ring structure A is a 5, 6 or 7-membered ring, which forms a benzene ring part and the fused ring (wherein the 5-, 6- or 7-membered ring that h R ¹¹ (R ¹¹ a halogen atom, a hydroxy group, a C _{1 -6} alkyl group (said alkyl group, a halogen atom, a hydroxy group, a cyano group, an amino group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkyl a carbonyl group, C _{1 -4} alkoxycarbonyl group (the alkoxy group, an alkylcarbonyloxy group, an alkyl-carbonyl group and alkoxycarbonyl group may be arbitrarily substituted with halogen atom) may also optionally be substituted.), C _{1 -6} alkoxy group (said alkoxy group, a halogen atom, a hydroxy group, a cyano group, an amino group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, C _{1 -4} alkoxycarbonyl group (the alkoxy group, alkylcarbonyl The oxy group, alkylcarbonylamino group and alkoxycarbonyl group may be optionally substituted with a halogen atom.), Nitro group, cyano group, formyl group, formamide group, carbamoyl group, sulfo group, a sulfonyl group, a sulfamoyl group, a sulfonyl group, amino group, carboxyl group, C _{1 - 6} alkylamino group, a di-C _{1 - 6} alkylamino group, C _{1 - 6} alkylcarbonyl group, C _{1 - 6} alkyl sulfonamide group, C _{6 - 14,} an aryl sulfonamide group, C _{1 - 6} alkylaminocarbonyl group, di C _{1 - 6} alkylaminocarbonyl group, C _{1 - 6} alkylcarbonyl group, C _{1 - 6} alkoxycarbonyl group, C _{1 - 6} alkylsulfonyl, C _{6 -14} aryl alkylsulfonyl group, or C _{6 -14} aryl group (the alkylamino group, a dialkylamino group, an alkyl carbonyl group, an alkyl sulfonamide group, a aryl sulfonamide group, an alkylaminocarbonyl group, if alkylaminocarbonyl group, the alkyl Viterbo the group, alkoxycarbonyl group, alkylsulfonyl group, arylsulfonyl group and the arylcarbonyl group may be arbitrarily substituted with halogen atom), and, h is an integer of 1-6, in the case of h is 2 to 6, and R ¹¹ are the same Or an oxygen atom, a nitrogen atom, or a sulfur atom alone or in combination, and the number of unsaturated bonds in the ring is condensed. A carbon atom constituting the ring containing an unsaturated bond of a benzene ring to be 1, 2 or 3, may be carbonyl or thiocarbonyl)), X in formula (13), Z of NR ²⁰ (R ^20, means a hydrogen atom or a C _{1 -4} alkyl group) represents a, Y in the formula (13), denotes a bond, SO or SO _2, formula 13, C _{1 -4} alkyl group (the alkyl group is from 1 to 5 halogen atom or Phenyl. _- means (the phenyl group, C _{1. 4} may be optionally substituted with an alkyl group) may also optionally be substituted with a) or phenyl group (the phenyl group may optionally be substituted by a C _{1 -4} alkyl group), and , formula (13) in W is a hydrogen atom, a hydroxy group, C _{1 - 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), halogen atom, C _{1 - 4} alkyl or C _{1 - 6} alkyl sulfone An amide group (the alkyl group and alkyl sulfone amide group may be optionally substituted with a halogen atom),

Expression (13) in the R ⁹ and R ¹⁰ are, each independently represent a hydrogen atom, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 - 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom). or may be by a hydroxy group optionally substituted) or C _{6 -14} aryl group (the aryl group, a halogen atom, a hydroxy group, a nitro group, a cyano group, C _{1 -6} alkyl group (said alkyl group, a halogen atom, a C _{1 - 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) or by a hydroxy group optionally may be substituted) or C _{1 -.. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) optionally substituted by May be substituted.)

Optically active chromium compound represented by the formula, formula (1), formula (1 '), formula (2), formula (2'), formula (3), formula (3 '), formula (4) and formula (4') The optically active titanium complex represented by) is dissolved in an organic solvent in a nitrogen atmosphere or in the air, and an oxidizing agent is added to the reaction solution and stirred to carry out a subsidiary epoxidation reaction, and the following formula (14) and formula (15) , Equation (16) or equation (17)

(Tue 20)

(Wherein R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , A, W, X, Y and Z are as described above. The absolute arrangement of the carbon atoms represented by * is (R) or (S It is a method of manufacturing the optically active chromium oxide compound shown by the following), and it can manufacture according to the method shown by following Reaction Formula 1.

(Tue 21)

Scheme 1 (wherein R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , A, W, X, Y and Z are the same as above. The absolute arrangement of carbon atoms represented by * is (R) Or (S).) Represents a formula by treating the chromium compound represented by formula (10), formula (11), formula (12) or formula (13) in a solvent with an oxidizing agent and an optically active titanium complex. The optically active chromium oxide compound represented by Formula (14) from (10), Formula (15) from Formula (11), Formula (16) from Formula (12), or Formula (17) from Formula (13). It shows a method of producing.

The chromate compound represented by said Formula (10), Formula (11), Formula (12), or Formula (13) which is a starting material of this invention can be synthesize | combined using the following general synthesis method of the benzopyran ring. Moreover, about the synthesis | combination of the condensed ring in Formula (11) and Formula (12), it is achieved by using suitably combining the synthesis method of the various heterocyclic rings shown below by the benzopyran ring synthesis method.

○ Benzopyran ring general synthesis method

Conventional methods (JM Ejans, et al., J. Med. Chem. 1984, 27, 1127., J. Med. Chem. 1986, 29, 2194., JT North, et al., J. Org.Chem 1995, 60, 3397., Japanese Patent Application Laid-Open No. 56-57785, Japanese Patent Application Laid-open No. 56-57786, Japanese Patent Application Laid-open No. 58-188880, Japanese Patent Application Laid-Open No. 2-141, Japan And the method described in JP-A-10-87650, JP-A-11-209366, and the like.

○ indole, oxyindole

Conventional methods (T. Sakamoto, et al., Heterocycles, 1986, 24, 31.

M. Belley, et al. , Synthesis, 2001, 222.

A. D. Cross, et al. , J. Chem. Soc. , 1961, 2714. et al.).

○ imidazolinone

Synthesis can be carried out according to existing methods (methods described in J. Kitteringham, et. Al., Synthetic® Commun., 2000, 30, 1937.).

○ quinoline

Conventional methods (S. Imor, et al., Synthetic Commun., 1996, 26, 2197.

Y. Kitahara, et al. , Tetrahedron, 1997, 53, 6001.

A. G. Osborne, et al. , J. Chem. Soc. Perkin Trans. 1993, 1, 181.

R. T. Shuman, et al. , J. Org. Chem. , 1990, 55, 738.

T. Sakamoto, et al. , Chem. Pharm. Bull. , 1981, 29, 2485.

Y. Tsuji, et al. , J. Org. Chem. , 1987, 52, 1673.

Z. Song, et al. , J. Heterocyclic® Chem. , 1993, 30, 17. and the like).

○ quinolinone

Conventional methods (M. R. Sabol, et al., Synthetic Commun., 2000, 30, 427.

Z-Y. Yang, et al. , Tetrahedron Lett. , 1999, 40, 4505.

H-B Sun, et al. , Synthesis, 1997, 1249.

A. Guiotto, et al. , J. Heterocyclic® Chem. , 1989, 26, 917.

K. Konno, et al. , Heterocycles, 1986, 24, 2169.

E. Fernandez, et al. , Synthesis, 1995, 1362. et al.).

○ benzothiazole, triazole,

Conventional methods (N. B. Ambati, et al., Synthetic Commun., 1997, 27, 1487.

D. E. Burton, et al. , J. Chem. Soc (C). , 1968, 1268. et al.).

Quinoxaline, quinoxalinone

Conventional methods (J. H. Liu, et al., J. Org. Chem., 2000, 65, 3395.

J. J. Li, et al. , Tetrahedron Lett. , 1999, 40, 4507.

Y. Ahmed, et al. , Bull. Chem. Soc. Jpn. , 1987, 60, 1145, etc.).

○ benzoxadinone

Conventional methods (G. H. Jones, et al., J. Med. Chem., 1987, 30, 295.

J. L. Wright, et al. , J. Med. Chem. , 2000, 43, 3408.

M. Kluge, et al. , J. Heterocyclic® Chem. , 1995, 32, 395. et al.).

The compound represented by following formula (35) and (36) is obtained by making compound (33) and compound (34) react. (Ref. Y. Tsuji, et al., J. Org. Chem., 1987, 52, 1673.)

(Tue 22)

The compounds represented by the following formulas (35) and (36) are obtained by reacting compound (33) with compound (37) in the presence of an acid catalyst. (Ref. Y. Kitahara, et al., Tetrahedron, 1997, 53, 6001. , Z. Song, et al., J. Heterocyclic chem., 1993, 30, 17.)

(Tue 23)

The chrome compound represented by the following formula (40) can be synthesized from compound (38), and is obtained by subsequently mesylating via compound (39) in which a nitro group is reduced to an amine by a platinum carbon catalyst.

(Tue 24)

Each substituent with respect to the chromate compound represented by said Formula (10), Formula (11), Formula (12), or Formula (13) is demonstrated concretely.

Each substituent of the said Formula (10) is demonstrated. (10) of the R ^5, R ^6, R ⁷ and R ⁸ are, each independently represent a hydrogen atom, a cyano group, a nitro group, a halogen atom, a C _{1 -4} alkyl group (said alkyl group, a halogen atom, a hydroxy group, a cyano group , nitro, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, C _{1 - 4} alkoxycarbonyl

(The alkoxy group, alkylcarbonyloxy group, alkylcarbonylamino group and alkoxycarbonyl group may be optionally substituted with a halogen atom.)

May be optionally substituted),

C _{1 - 4} alkoxy group

(Wherein the alkoxy group, a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, C _{1 -4} alkoxycarbonyl group (the The alkoxy group, the alkylcarbonyloxy group, the alkylcarbonylamino group and the alkoxycarbonyl group may be optionally substituted with a halogen atom.)

. As optionally may be substituted), C _{1 -4} alkyl-carbonyl group (the alkylcarbonyl group is a halogen atom, C _{6 -10} aryl group (the C _{6 - 10} aryl group is a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 - 4} alkyl, or C _{1 -. 4} may be an optionally substituted alkoxy group), may also optionally be substituted with a), C _{1 -. 4} alkyl-carbonyl (N-C _{1 - 4} alkyl) amino group ( the alkylcarbonyl (N- alkyl) amino group which may be optionally substituted with a halogen atom.), C _{1- 4} alkoxy group (the alkoxy group, there may be optionally substituted with a halogen atom.), C _{6 -10} aryl carboxylic carbonyl group (said aryl carbonyl amino group, a halogen atom, C _{1 -4} alkyl, C _{1 -. 4} alkoxy group, a cyano group or a nitro group may also optionally be substituted), C _{6 -1 0} arylcarbonyl (N- C _{1 - 4} alkyl) amino group (the arylcarbonyl (N- Alkyl) amino group, a halogen atom, C _{1 - 4} alkyl, C _{1 -. 4} alkoxy group, a cyano group or a nitro group optionally may be substituted), benzyl carbonyl group, a formyl group, a carbamoyl group, C _{1 -4} alkylsulfonyl group (wherein the alkylsulfonyl group may be arbitrarily substituted with halogen atom), C _{6 -10} aryl sulfonyl group (the aryl sulfonyl group, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or a nitro group optionally may be substituted), sulfamoyl group, C _{1 -. 4} alkyl sulfone amide group, C _{6 -10} aryl sulfonamide group (said alkyl group, and a sulfonamide group and the aryl sulfonamide, halogen atom, C _{1 - 4} alkyl, C _{1 -. 4} alkoxy group, a cyano group or a nitro group optionally may be substituted), an alkyl sulfone of beads already deugi (C _1-4 alkyl sulfone) already deugi (the beads (alkyl sulfone) is a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, when May be optionally substituted with a group or a nitro group), a bead. (C _{6 - 10} aryl sulfone) already deugi (the beads (aryl sulfone) already aryl sulfone of deugi is a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or a nitro group optionally may be substituted), [N, N. ' - (C 1 - 4 alkyl sulfone) (C _{6 - 10} aryl sulfone) imide group (the [N, N' - ( alkyl sulfone) (aryl sulfone) and sulfonated alkyl aryl sulfone of the already deugi is a halogen atom, C _{1 -. 4} alkyl, C _{1- 4} alkoxy group, a cyano group may, optionally be substituted with a nitro group) it shows a.

Each substituent of R <^5> , R <^6> , R <^7> and R <^8> in Formula (10) is demonstrated concretely.

As said halogen atom, a fluorine atom, a chlorine atom, a bromine atom, and an oxo atom are mentioned,

The C _{1 - 4} group include methyl group, trifluoromethyl group, methyl group, trichloromethyl n- propyl, i- propyl, c- propyl, n- butyl, i- butyl, s- butyl, t- butyl group and c- butyl group can be mentioned, wherein the C _{1 - 4} alkoxy group includes a methoxy group, trifluoromethyl, methoxy, trichloromethyl Romero Messenger, ethoxy, n- propoxy, i- propoxy time, c- propoxy, n- butoxy, i- butoxy, s- butoxy group, t- butoxy group, and c- may be made of a butoxy group or the like, the C _{1 - 4} As the alkylcarbonyl group, methyl Carbonylamino group, trifluoromethylcarbonylamino group, trichloromethylcarbonylamino group, ethylcarbonylamino group, n-propylcarbonylamino group, i-propylcarbonylamino group, c-propylcarbonylamino group, n-butylcarbonylamino group , i-butylcarbonylamino group, s-part Tylcarbonylamino group, t-butylcarbonylamino group, c-butylcarbonylamino group, p-methoxyphenylmethylcarbonylamino group, p-nitrophenylmethylcarbonylamino group, p-methoxyphenylethylcarbonylamino group, etc. the number, and the C _{1 -4-alkyl-carbonyl-As} (N-C _{1 4} alkyl) amino group, methyl-carbonyl (N- methyl) amino group, a trifluoromethyl-carbonyl (N- methyl) amino, methyl-carbonyl ( N-ethyl) amino group, trifluoromethylcarbonyl (N-ethyl) amino group, ethylcarbonyl (N-ethyl) amino group, n-propylcarbonyl (N-ethyl) amino group, i-propylcarbonyl (N-ethyl) Amino group, c-propylcarbonyl (N-ethyl) amino group, n-butylcarbonyl (N-ethyl) amino group, i-butylcarbonyl (N-ethyl) amino group, s-butylcarbonyl (N-ethyl) amino group, t-butylcarbonyl (N-ethyl) amino group and c-butylcarbonyl (N-ethyl) It may be made of diamino group or the like, the C _{1 - 4} alkoxy group, a methoxy group, a trifluoromethoxy group, ethoxy group, n- propoxy group, i- propoxy group, a c- propoxy group, n -butoxycarbonyl group, i- butoxy group, a s- butoxy group, t- butoxy group, and as c- and the like butoxycarbonyl group, the C _{6 -10} aryl-carbonyl group, a phenyl-carbonyl group, 1-naphthyl-carbonyl group and a 2-naphthyl-carbonyl group and the like can be mentioned, wherein the C _{6 - 10} aryl-carbonyl (N-C _{1 - 4} alkyl) amino groups as the phenyl-carbonyl (N- methyl) amino group , phenyl-carbonyl (N- ethyl) amino group, 1-naphthyl-carbonyl (N- ethyl) amino group and a 2-naphthyl-carbonyl (N- ethyl) may be made of an amino group or the like, the C _{1 - 4} alkylsulfonyl group As Methanesulfonyl group, trifluoromethanesulfonyl group, ethanesulfonyl group, n-propanesulfonyl group, i-propanesulfonyl group, c-propanesulfonyl group, n-butanesulfonyl group, i-butanesulfonyl group, s-butanesulfonyl group, t- butane sulfonyl group and c- butane sulfonate group or the like can be mentioned, wherein the C _{6 -1 0} As the aryl sulfonate group, a benzene sulfonyl group, p- fluoro benzene sulfonyl group, p- Trois yen sulfonyl, 1-naphthalene sulfonate group and a naphthalene-2-sulfonyl group or the like can be mentioned, wherein the C _{1 - 4} Al skill sulfonamide group include methane sulfonamide group, a trifluoromethane sulfone amide group, a sulfonamide group ethane, n- propane sulfonamide group, i-propanesulfonamide group, c-propanesulfonamide group, n-butanesulfonamide group, i-butanesulfonamide group, s-butanesulfonamide group, t-butanesulfonamide group and c-butanesulfonamide group there may be mentioned, wherein the C _{6 - 10} aryl group as a sulfonamide group ,

Benzenesulfonamide group, a p- fluorine benzenesulfonamide group, p- toluenesulfonamide group, a 1-naphthalene sulfonamide group and a 2-naphthalene sulfonamide and amide group or the like, the bead (C _{1 - 4} alkyl sulfone) already Examples of the beads include beads (methane sulfone) imide groups, beads (trifluoro methane sulfone) imide groups, beads (ethane sulfone) imide groups, beads (n-propane sulfone) imide groups, beads (i-propane sulfone) imide groups, beads (c-propane sulfone) imide group, beads (n-butane sulfone) imide group, beads (i-butane sulfone) imide group, beads (s-butane sulfone) imide group, beads (t-butane sulfone) imide group and beads (c- butane sulfone) and the like are already deugi, the beads (C _{6 - 10} aryl sulfone) As already deugi, beads (benzenesulfonamide), already deugi, beads (p- fluoro benzenesulfonamide), already deugi, beads (p -Toluene sulfone) imide group, beads (1-naphthalene sulfone) imide group, and beads (2-naphthalene sulfone) imide And the like group, the [N, N '- (C 1 - 4 alkyl sulfone) (C _{6 -10} aryl sulfone)] As the imide group, [N, N' - (methane) (benzene)] imide group , [N, N '-(trifluoromethane) (benzene)] imide group, [N, N'-(trifluoromethane) (p-fluorobenzene)] imide group, [N, N '-(ethane) ( Benzene)] imide group, [N, N'- (methane) (p-toluene)] imide group, [N, N'- (trifluoromethane) (p-toluene)] imide group, [N, N'- (Ethane) (p-toluene)] imide group, [N, N '-(methane) (1-naphthalene)] imide group, [N, N'-(trifluoromethane) (1-naphthalene)] imide group , [N, N'- (ethane) (1-naphthalene)] imide group, [N, N'- (methane) (2-naphthalene)] imide group, [N, N'- (trifluoromethane) (2 -Naphthalene)] imide group, a [N, N '-(ethane) (2-naphthalene)] imide group, etc. are mentioned.

In formula (10), R ⁵ and R ⁶ each independently represent a hydrogen atom, a cyano group, a nitro group, a fluorine atom, a chlorine atom, a bromine atom, an oxo atom, a methyl group, a trifluoromethyl group, an ethyl group, an n-propyl group, and i -Propyl group, c-propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group, c-butyl group, methoxy group, trifluoro methoxy group, ethoxy group, n-propoxy group , i-propoxy group, c-propoxy group, n-butoxy group, i-butoxy group, s-butoxy group, t-butoxy group, c-butoxy group, methylcarbonylamino group, trifluoromethylcarbonylamino group, Ethylcarbonylamino group, n-propylcarbonylamino group, i-propylcarbonylamino group, c-propylcarbonylamino group, n-butylcarbonylamino group, i-butylcarbonylamino group, s-butylcarbonylamino group, t-butyl Carbonylamino group, c-butylcarbonylamino group, methylcarbonyl (N-methyl) amino No group, trifluoromethylcarbonyl (N-methyl) amino group, methylcarbonyl (N-ethyl) amino group, trifluoromethylcarbonyl (N-ethyl) amino group, ethylcarbonyl (N-ethyl) amino group, n-propyl carbon Carbonyl (N-ethyl) amino group, i-propylcarbonyl (N-ethyl) amino group, c-propylcarbonyl (N-ethyl) amino group, n-butylcarbonyl (N-ethyl) amino group, i-butylcarbonyl ( N-ethyl) amino group, s-butylcarbonyl (N-ethyl) amino group, t-butylcarbonyl (N-ethyl) amino group, c-butylcarbonyl (N-ethyl) amino group, methoxycarbonyl group, trifluoromethoxy Carbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, i-propoxycarbonyl group, phenylcarbonylamino group, 1-naphthylcarbonylamino group, 2-naphthylcarbonylamino group, phenylcarbonyl (N-methyl) amino group, phenyl Carbonyl (N-ethyl) amino group, 1-naph Carbonyl (N-ethyl) amino group, 2-naphthylcarbonyl (N-ethyl) amino group, benzylcarbonylamino group, formyl group, carbamoyl group, methane sulfone amide group, trifluoromethane sulfone amide group, ethane sulfone amide group , n-propane sulfone amide group, i-propane sulfone amide group, c-propane sulfone amide group, n-butane sulfone amide group, i-butane sulfone amide group, s-butane sulfone amide group, t-butane sulfone amide group, c-butane sulfone amide group, beads (methane sulfone) imide group, beads (trifluoro methane sulfone) imide group, beads (ethane sulfone) imide group, beads (n-propane sulfone) imide group, beads (i-propane sulfone) Imide group, beads (c-propane sulfone) imide group, beads (n-butane sulfone) imide group, beads (i-butane sulfone) imide group, beads (s-butane sulfone) imide group, beads (t-butane sulfone) Imide group, beads (c-butane sulfone) imide group, beads (benzene Fone) imide group, bead (p-toluene sulfone) imide group, bead (1-naphthalene sulfone) imide group, bead (2-naphthalene sulfone) imide group, [N, N'- (methane) (benzene)] imide group , [N, N '-(trifluoromethane) (benzene)] imide group, [N, N'-(ethane) (benzene)] imide group, [N, N '-(methane) (p-toluene)] Imide group, [N, N '-(trifluoromethane) (p-toluene)] imide group, [N, N'-(ethane) (p-toluene)] imide group, [N, N '-(methane) (1-naphthalene)] imide group, [N, N '-(trifluoromethane) (1-naphthalene)] imide group, [N, N'-(ethane) (1-naphthalene)] imide group, [N, N '-(methane) (2-naphthalene)] imide group, [N, N'-(trifluoromethane) (2-naphthalene)] imide group, [N, N '-(ethane) (2-naphthalene)] Imide group is preferable, More preferably, a hydrogen atom, a nitro group, a fluorine atom, a chlorine atom, a methoxy group, methylcarbonylami No group, methyl carbonyl (N-ethyl) amino group, bead (trifluoro methane sulfone) imide group, [N, N'- (trifluoro methane) (benzene)] imide group, [N, N'- (trifluoro methane) ) (p-toluene)] imide group.

In formula (10), R ⁷ represents a hydrogen atom, a cyano group, a nitro group, a methane sulfone amide group, a trifluoromethane sulfone amide group, an ethane sulfone amide group, an n-propane sulfone amide group, an i-propane sulfone amide group, c -Propane sulfone amide group, n-butane sulfone amide group, i-butane sulfone amide group, s-butane sulfone amide group, t-butane sulfone amide group, c-butane sulfone amide group, beads (methane sulfone) imide group, beads (Trifluoromethane sulfone) imide group, beads (ethane sulfone) imide group, beads (n-propane sulfone) imide group, beads (i-propane sulfone) imide group, beads (c-propane sulfone) imide group, beads (n -Butane sulfone imide group, beads (i-butane sulfone) imide group, beads (s-butane sulfone) imide group, beads (t-butane sulfone) imide group, beads (c-butane sulfone) imide group, beads (benzene Sulfone) imide group, beads (p-toluene sulfone) imide group, beads (1-naphthalene sulfone) Imide group, beads (2-naphthalene sulfone) imide group, [N, N'- (methane) (benzene)] imide group, [N, N'- (trifluoro methane) (benzene)] imide group, [N, N '-(trifluoromethane) (p-fluorobenzene)] imide group, [N, N'-(ethane) (benzene)] imide group, [N, N '-(methane) (p-toluene)] imide Rare, [N, N '-(trifluoromethane) (p-toluene)] imide group, [N, N'-(ethane) (p-toluene)] imide group, [N, N '-(methane) ( 1-naphthalene)] imide group, [N, N'- (trifluoromethane) (1-naphthalene)] imide group, [N, N '-(ethane) (1-naphthalene)] imide group, [N, N V- (methane) (2-naphthalene)] imide group, [N, N- (trifluoromethane) (2-naphthalene)] imide group, [N, N '-(ethane) (2-naphthalene)] imide group Dehydration is preferable, More preferably, a hydrogen atom, a nitro group, a bead (methane sulfone) imide group, a bead (trifluoro methane sulfone) Imide group, [N, N '- (trifluoromethanesulfonate) (benzene)] imide group, [N, N' - (trifluoromethanesulfonate) (p- toluene)] represents an imide.

In formula (10), R <^8> is a hydrogen atom, a fluorine atom, a chlorine atom, a cyano group, a nitro group, a methyl group, a trifluoromethyl group, an ethyl group, n-propyl group, i-propyl group, c-propyl group, n-butyl Group, i-butyl group, s-butyl group, t-butyl group, and c-butyl group are preferable, More preferably, they are a hydrogen atom, a fluorine atom, a nitro group, a methyl group, and a trifluoromethyl group.

(10) of the R ⁹ and R ¹⁰ are each independently a hydrogen atom, a C _{1 -6} alkyl group (said alkyl group, a halogen atom, and may be arbitrarily substituted with C _{1 -6} alkoxy group (said alkoxy group is a halogen atom.) Or may be optionally substituted by a hydroxy group) or a C _{6 -. 14} aryl group

(Wherein the aryl group, a halogen atom, a hydroxy group, a nitro group, a cyano group, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 -. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) or hydroxy group on may also optionally be substituted.) or a C _{1 -6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) may also optionally be substituted by a) it shows a.

Each substituent of R <^9> and R <^10> in Formula (10) is demonstrated concretely. Examples of the C _{1 -6} alkyl group, a methyl group, a trifluoro methyl group, ethyl group, n- propyl, i- propyl, n- butyl, i- butyl, s- butyl, t- butyl, 1-pentyl group , 2-pentyl group, 3-pentyl group, i-pentyl group, neopentyl group, 2, 2-dimethyl propyl group, 1-hexyl group, 2-hexyl group, 3-hexyl group, 1-methyl-n-pen group, can be exemplified by 1, 1,2-trimethyl -n- propyl, 1,2, 2-trimethyl -n- propyl group and a 3, 3-dimethyl -n- butyl group, the C _{6 -} Examples of the ₁₄ aryl group include a phenyl group, an o-biphenylyl group, an m-biphenylyl group, a p-biphenylyl group, a 1-naphthyl group, a 2-naphthyl group, a 1-anthryl group, a 2-anthryl group, and a 9-an And triphenyl group, 1-phenanthryl group, 2-phenanthryl group, 3-phenanthryl group, 4-phenanthryl group, and 9-phenanthryl group.

R ^{9 in} formula (10) And R ¹⁰ is preferably a hydrogen atom, a methyl group, a trifluoromethyl group, an ethyl group, or a phenyl group, and more preferably a methyl group.

Each substituent in Formula (11) and Formula (12) is demonstrated.

(11) and (12) of the R ⁹ and R ¹⁰ are, each independently represent a hydrogen atom, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 - 6} optionally substituted alkoxy group (the alkoxy group is a halogen atom may be.), or by a hydroxy group optionally may be substituted.) or a C _{6 -14} aryl group (the aryl group, a halogen atom, a hydroxy group, a nitro group, a cyano group, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 -. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) or may be optionally substituted by a hydroxy group) or a C _{1 -6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom May be optionally substituted with.).

Each substituent of R <^9> and R <^10> in Formula (11) and Formula (12) is demonstrated concretely.

Examples of the C _{1 -6} alkyl group, a methyl group, a trifluoro methyl group, ethyl group, n- propyl, i- propyl, n- butyl, i- butyl, s- butyl, t- butyl, 1-pentyl group , 2-pentyl group, 3-pentyl group, i-pentyl group, neopentyl group, 2, 2-dimethyl propyl group, 1-hexyl group, 2-hexyl group, 3-hexyl group, 1-methyl-n-pen group, may be made of 1, 1, 2-trimethyl -n- propyl, 1,2, 2-trimethyl -n- propyl group and a 3, 3-dimethyl -n- butyl group, the C _{6 -} Examples of the ₁₄ aryl group include a phenyl group, an o-biphenylyl group, an m-biphenylyl group, a p-biphenylyl group, a 1-naphthyl group, a 2-naphthyl group, a 1-anthryl group, a 2-anthryl group, and a 9-an And triphenyl group, 1-phenanthryl group, 2-phenanthryl group, 3-phenanthryl group, 4-phenanthryl group, and 9-phenanthryl group.

R ⁹ in formulas (11) and (12) And R ¹⁰ is preferably a hydrogen atom, a methyl group, a trifluoromethyl group, an ethyl group, or phenyl, and more preferably a methyl group.

The partial ring structure A in Formulas (11) and (12) will be described. Partial ring structure A is a 5, 6 or 7 membered ring which forms a condensed ring with the benzene ring moiety.

(The 5, 6 or 7 membered ring is all h R ¹¹

(R ¹¹ is a halogen atom, a hydroxy group, a C1-6 alkyl group.

(Said alkyl group, a halogen atom, a hydroxy group, a cyano group, an amino group, a nitro group, C _{1- 4} alkoxy group, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, C _{1 - 4} alkoxycarbonyl

(The alkoxy group, alkylcarbonyloxy group, alkylcarbonylamino group and alkoxycarbonyl group may be optionally substituted with a halogen atom.)

May be optionally substituted),

C _{1 -6} alkoxy

(Wherein the alkoxy group, a halogen atom, a hydroxy group, a cyano group, an amino group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, C _{1 - 4} alkoxycarbonyl

(The alkoxy group, alkylcarbonyloxy group, alkylcarbonylamino group and alkoxycarbonyl group may be optionally substituted with a halogen atom.)

May be optionally substituted),

A nitro group, a cyano group, a formyl group, forms an amide group, a carbamoyl group, sulfo group, sulfonyl group, sulfamoyl group, sulfonyl group, amino group, carboxyl group, C _{1 - 6} alkylamino group, a di-C _{1 - 6} alkylamino group, C _{1 - 6} alkylcarbonyl group, C _{1 - 6} alkyl sulfonamide group, C _{6 - 14} aryl sulfonamide group, C _{1 - 6} alkylaminocarbonyl group, di-C _{1 -6} alkylamino group, a C _{1 - 6} alkylcarbonyl group, C _{1 - 6} alkoxycarbonyl group, C _{1 - 6} alkylsulfonyl, C _{6 - 14} arylsulfonyl group, or a C _{6 - 14} aryl group

(The alkyl amino group, dialkylamino group, alkylcarbonylamino group, alkyl sulfone amide group, aryl sulfone amide group, alkylaminocarbonyl group, dialkylaminocarbonyl group, alkylcarbonyl group, alkoxycarbonyl group, alkylsulfonyl group, arylsulfonyl group and arylcarbonyl group May be optionally substituted with a halogen atom.)

H is an integer of 1 to 6, and when h is 2 to 6, R ¹¹ may be the same or different.)

It may be optionally substituted by, and may include an oxygen atom, a nitrogen atom or a sulfur atom alone or in combination as a constituent atom of the ring, the number of unsaturated bonds in the ring, the unsaturated bond of the benzene ring condensed It is 1, 2 or 3, and the carbon atoms constituting the ring may be carbonyl or thiocarbonyl.)

It means a partial structure represented by.

The above R ¹¹ will be described in detail.

Examples of the halogen atom include fluorine atom, chlorine atom, bromine atom and oxo atom.

The C _{1 - 6} alkyl group as a methyl, trifluoro methyl, ethyl, n- propyl, i- propyl, n- butyl, i- butyl, s- butyl, t- butyl, 1-pentyl group , 2-pentyl group, 3-pentyl group, i-pentyl group, neopentyl group, 2, 2-dimethyl propyl group, 1-hexyl group, 2-hexyl group, 3-hexyl group, 1-methyl-n-pen Tyl group, 1, 1, 2-trimethyl-n-propyl group, 1, 2, 2-trimethyl-n-propyl group, 3, 3- dimethyl- n-butyl group, methylcarbonyloxymethyl group, ethylcarbonyl Oxymethyl group, methylcarbonyloxyethyl group, ethylcarbonyloxyethyl group, methylcarbonylaminomethyl group, trifluoromethylcarbonylaminomethyl group, ethylcarbonylaminomethyl group, methylcarbonylaminoethyl group, ethylcarbonylaminoethyl group, methoxycarbon Carbonylmethyl group, trifluoromethoxycarbonylmethyl group, ethoxycarbonylmethyl group, methoxycarbonylethyl group and ethoxycarbonyl It can include a group such as,

The C _{1 - 6} alkoxy group includes a methoxy group, trifluoromethyl, methoxy, ethoxy, n- propoxy, i- propoxy, n- butoxy, i- butoxy, s- butoxy group, t- butoxy Period, 1-pentyl oxy, 2-pentyl oxy, 3-pentyl oxy, i-pentyl oxy, neopentyl oxy, 2, 2- dimethyl propoxy, 1-hexyl oxy, 2-hexyl oxy , 3-hexyl oxy group, 1-methyl-n-pentyl oxy group, 1, 1, 2-trimethyl-n-propoxy group, 1, 2, 2-trimethyl-n-propoxy group, 3, 3 -Dimethyl-n-butoxy group, methylcarbonyloxymethoxy group, ethylcarbonyloxymethoxy group, methylcarbonyloxyethoxy group, ethylcarbonyloxyethoxy group, methylcarbonylaminomethoxy group, trifluoromethylcarbonyl Aminomethoxy group, ethylcarbonylaminomethoxy group, methylcarbonylaminoethoxy group, ethylcarbonylaminoethoxy group, methoxycarbonylmethoxy group, tri Fluoromethoxycarbonylmethoxy group, ethoxycarbonylmethoxy group, methoxycarbonylethoxy group, ethoxycarbonylethoxy group, etc. may be mentioned,

The C _{1 - 6} alkyl as an amino group, a methylamino group, trifluoromethyl group, ethylamino group, n- propylamino group, i- propyl group, a c- propyl group, a n- butyl group, i- butyl group, a s- butyl group, t-butyl amino group, c-butyl amino group, 1-pentyl amino group, 2-pentyl amino group, 3-pentyl amino group, i-pentyl amino group, neopentyl amino group, t-pentyl amino group, c-pentyl amino group, 1-hexyl amino group, 2 -Hexyl amino group, 3-hexyl amino group, c-hexyl amino group, 1-methyl-n-pentyl amino group, 1, 1, 2-trimethyl-n-propyl amino group, 1, 2, 2-trimethyl-n-propyl amino group And a 3, 3- dimethyl- n-butyl amino group etc. are mentioned,

Examples of the di-C _{1 -6} alkylamino group, a dimethylamino group, a di- (trifluoromethyl) amino group, di-ethylamino group, di -n- propyl group, a di--i- propylamino group, di-c- propyl group, a di- n-butyl amino group, di-i-butyl amino group, di-s-butyl amino group, di-t-butyl amino group, di-c-butyl amino group, di-1-pentyl amino group, di-2-pentyl amino group, di-3 -Pentyl amino group, di-i-pentyl amino group, dinepentylamino group, di-t-pentyl amino group, di-pentyl amino group, di-hexyl amino group, di-2-hexyl amino group, di-hexyl amino group , Di-c-hexyl amino group, di- (1-methyl-n-pentyl) amino group, di (1, 1, 2-trimethyl-n-propyl) amino group, di (1, 2, 2-trimethyl-n -Propyl) amino group, di (3, 3-dimethyl- n-butyl) amino group, methyl (ethyl) amino group, methyl (n-propyl) amino group, methyl (i- Lofil) amino group, methyl (c-propyl) amino group, methyl (n-butyl) amino group, methyl (i-butyl) amino group, methyl (s-butyl) amino group, methyl (t-butyl) amino group, methyl (c-butyl) Amino group, ethyl (n-propyl) amino group, ethyl (i-propyl) amino group, ethyl (c-propyl) amino group, ethyl (n-butyl) amino group, ethyl (i-butyl) amino group, ethyl (s-butyl) amino group, Ethyl (t-butyl) amino group, ethyl (c-butyl) amino group, n-propyl (i-propyl) amino group, n-propyl (c-propyl) amino group, n-propyl (n-butyl) amino group, n-propyl ( i-butyl) amino group, n-propyl (s-butyl) amino group, n-propyl (t-butyl) amino group, n-propyl (c-butyl) amino group, i-propyl (c-propyl) amino group, i-propyl ( n-butyl) amino group, i-propyl (i-butyl) amino group, i-propyl (s-butyl) amino group, i-propyl (t-butyl) amino group, i-propyl ( c-butyl) amino group, c-propyl (n-butyl) amino group, c-propyl (i-butyl) amino group, c-propyl (s-butyl) amino group, c-propyl (t-butyl) amino group, c-propyl ( c-butyl) amino group, n-butyl (i-butyl) amino group, n-butyl (s-butyl) amino group, n-butyl (t-butyl) amino group, n-butyl (c-butyl) amino group, i-butyl ( s-butyl) amino group, i-butyl (t-butyl) amino group, i-butyl (c-butyl) amino group, s-butyl (t-butyl) amino group, s-butyl (c-butyl) amino group and t-butyl ( c-butyl) amino group, etc. are mentioned,

The C _{1 -6} alkylcarbonyl As the amino group, methyl-carbonyl group, a trifluoromethyl-carbonyl group, ethyl carbonyl group, propyl carbonyl group n-, i- propyl carbonyl group, an n- butyl carbonyl group, i -Butylcarbonylamino group, s-butylcarbonylamino group, t-butylcarbonylamino group, 1-pentylcarbonylamino group, 2-pentylcarbonylamino group, 3-pentylcarbonylamino group, i-pentylcarbonylamino group, neopentyl A carbonylamino, t-pentylcarbonylamino group, 1-hexylcarbonylamino group, 2-hexylcarbonylamino group, 3-hexylcarbonylamino group, etc. are mentioned,

The C _{1 - 6} alkyl sulfone as an amide group, a methanesulfonamide group, a trifluoro methane sulfone amide group, a sulfonamide group ethane, n- propane sulfone amide group, a sulfonamide group i- propane, n- butane sulfonamide group, an i -Butane sulfone amide group, s-butane sulfone amide group, t-butane sulfone amide group, 1-pentane sulfamide group, 2-pentane sulfonamide group, 3-pentane sulfonamide group, i-pentane sulfonamide group, neopentane A sulfonamide group, a t-pentane sulfonamide group, a 1-hexane sulfone amide group, a 2-hexane sulfone amide group, a 3-hexane sulfone amide group, etc. are mentioned,

The C _{6 - 14} aryl group includes a sulfonamide, benzene sulfonamide group, p- toluenesulfonamide group, an o- biphenyl sulfonamide group, a sulfone amide group ratio m-, p- biphenyl sulfonamide group, a 1-naphthalene Sulfonamide group, 2-naphthalene sulfone amide group, 1-anthracene sulfonamide group, 2-anthracene sulfonamide group, 9-anthracene sulfonamide group, 1-phenanthrene sulfonamide group, 2-phenanthrene sulfonamide group, 3- Phenanthrene sulfonamide group, 4-phenanthrene sulfonamide group, 9-phenanthrene sulfonamide group, etc. are mentioned,

The C _{1 - 6} Examples of alkylamino group, a methylamino group, trifluoromethyl amino group, ethylamino group, n- propylamino group, an i- profile aminocarbonyl group, n- butylamino group, i- butylamino group, s -Butylaminocarbonyl group, t-butylaminocarbonyl group, 1-pentylaminocarbonyl group, 2-pentylaminocarbonyl group, 3-pentylaminocarbonyl group, i-pentylaminocarbonyl group, neopentylaminocarbonyl, t-pentylaminocarbonyl group, 1-hexyl Aminocarbonyl group, 2-hexylaminocarbonyl group, 3-hexylaminocarbonyl group, etc. are mentioned,

The di C _{1 -} Examples ₆ alkylamino group, a dimethylamino group, a member (trifluoromethyl) amino group, if ethylamino group, a di -n- propylamino group, a di -i- propylamino group, di-propyl -c- Aminocarbonyl group, di-n-butylaminocarbonyl group, di-i-butylaminocarbonyl group, di-s-butylaminocarbonyl group, t-butylaminocarbonyl group, di-c-butylaminocarbonyl group, di-1 -pentylaminocarbonyl group, Di-2-pentylaminocarbonyl group, di-3-pentylaminocarbonyl group, di-i-pentylaminocarbonyl group, dineopentylaminocarbonyl group, di-t-pentylaminocarbonyl group, di-c-pentylaminocarbonyl group, di-1- Hexylaminocarbonyl group, di-2-hexylaminocarbonyl group, di-3-hexylaminocarbonyl group, di-c-hexylaminocarbonyl group, di (1-methyl-n-pentyl) aminocar Carbonyl group, di (1, 1, 2-trimethyl- n-propyl) aminocarbonyl group, G (1, 2, 2-trimethyl- n-propyl) aminocarbonyl group, di (3, 3- dimethyl- n-butyl ) Aminocarbonyl group, methyl (ethyl) aminocarbonyl group, trifluoromethyl (ethyl) aminocarbonyl group, methyl (n-propyl) aminocarbonyl group, methyl (i-propyl) aminocarbonyl group, methyl (c-propyl) aminocarbonyl group, methyl (n -Butyl) aminocarbonyl group, methyl (i-butyl) aminocarbonyl group, methyl (s-butyl) aminocarbonyl group, methyl (t-butyl) aminocarbonyl group, methyl (c-butyl) aminocarbonyl group, ethyl (n-propyl) amino Carbonyl group, ethyl (i-propyl) aminocarbonyl group, ethyl (c-propyl) aminocarbonyl group, ethyl (n-butyl) aminocarbonyl group, ethyl (i-butyl) aminocarbonyl group, ethyl (s-butyl) aminocarbonyl group, ethyl (t -Butyl) aminocarbonyl Group, ethyl (c-butyl) aminocarbonyl group, n-propyl (i-propyl) aminocarbonyl group, n-propyl (c-propyl) aminocarbonyl group, n-propyl (n-butyl) aminocarbonyl group, n-propyl (i- Butyl) aminocarbonyl group, n-propyl (s-butyl) aminocarbonyl group, n-propyl (t-butyl) aminocarbonyl group, n-propyl (c-butyl) aminocarbonyl group, i-propyl (c-propyl) aminocarbonyl group, i -Propyl (n-butyl) aminocarbonyl group, i-propyl (i-butyl) aminocarbonyl group, i-propyl (s-butyl) aminocarbonyl group, i-propyl (t-butyl) aminocarbonyl group, i-propyl (c-butyl ) Aminocarbonyl group, c-propyl (n-butyl) aminocarbonyl group, c-propyl (i-butyl) aminocarbonyl group, c-propyl (s-butyl) aminocarbonyl group, c-propyl (t-butyl) aminocarbonyl group, c- Propyl (c-butyl) aminocarbonyl group, n- Tyl (i-butyl) aminocarbonyl group, n-butyl (s-butyl) aminocarbonyl group, n-butyl (t-butyl) aminocarbonyl group, n-butyl (c-butyl) aminocarbonyl group, i-butyl (s-butyl) Aminocarbonyl group, i-butyl (t-butyl) aminocarbonyl group, i-butyl (c-butyl) aminocarbonyl group, s-butyl (t-butyl) aminocarbonyl group, s-butyl (c-butyl) aminocarbonyl group and t-butyl (c-butyl) aminocarbonyl group, etc. are mentioned,

The C _{1 - 6} as the alkyl group, methyl group, trifluoromethyl group, ethyl group, n- propyl group, i- propyl group, a n- butyl group, i- butyl group, a s- butyl group, a t- butyl group, 1-pentyl carbonyl group, 2-pentyl carbonyl group, 3-pentyl carbonyl group, i-pentyl carbonyl group, neopentyl carbonyl group, t-pentyl carbonyl group, 1-hexyl carbonyl group, 2-hexyl carbonyl group, and 3-hexyl carbonyl group, etc. are mentioned,

The C _{1 - 6} alkoxy group, a methoxy group, a trifluoromethoxy group, ethoxy group, n- propoxy group, i- propoxy group, n- butoxycarbonyl group, butoxycarbonyl group i-, s- portion Oxycarbonyl group, t-butoxycarbonyl group, 1-pentyloxycarbonyl group, 2-pentyloxycarbonyl group, 3-pentyloxycarbonyl group, i-pentyloxycarbonyl group, neopentyloxycarbonyl group, t-pentyloxycarbonyl group, 1-hexyloxycarbonyl group, 2-hexyloxycarbonyl group, 3-hexyloxycarbonyl group, etc. are mentioned,

The C _{1 - 6} As the alkylsulfonyl group, and the like methanesulfonyloxy group, trifluoro methane sulfonyl group, ethane sulfonyl group, propane sulfonyl group and n- n- butane sulfonyl group,

The C _{6 - 14} arylsulfonyl group as benzene sulfonyl group, p- fluoro benzene sulfonyl group, p- Trois yen sulfonyl group, o- biphenyl sulfonyl group, m--biphenyl sulfonyl group, p- biphenyl sulfonyl group, 1 -Naphthalenesulfonyl group, 2-naphthalenesulfonyl group, 1-anthracenesulfonyl group, 2-anthracenesulfonyl group, 9-anthracenesulfonyl group, 1-phenanthrenesulfonyl group, 2-phenanthrenesulfonyl group, 3-phenanthrene sulfonyl group , 4-phenanthrene sulfonyl group, 9-phenanthrene sulfonyl group, etc. are mentioned,

The C _{6 - 14} aryl group Examples of the phenyl group, a p- fluorophenyl group, a biphenyl group o-, m- biphenyl group, p- biphenyl group, a 1-naphthyl group, a 2-naphthyl group, 1- Anthricarbonyl group, 2-Anthricarbonyl group, 9-Anthricarbonyl group, 1-phenanthryl carbonyl group, 2-phenanthryl carbonyl group, 3-phenanthryl carbonyl group, 4-phenanthryl carbonyl group, and 9-phenan Tricarbonyl group etc. are mentioned.

About said R <^11> , a preferable atom and substituent are demonstrated concretely.

R ¹¹ is a fluorine atom, chlorine atom, bromine atom, methyl group, trifluoromethyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, n-pentyl group, i-pentyl group, 3, 3- Dimethyl-n-butyl group, methylcarbonyloxymethyl group, ethylcarbonyloxymethyl group, methylcarbonyloxyethyl group, ethylcarbonyloxyethyl group, methylcarbonylaminomethyl group, trifluoromethylcarbonylaminomethyl group, ethylcarbonylaminomethyl group , Methylcarbonylaminoethyl group, ethylcarbonylaminoethyl group, methoxycarbonylmethyl group, trifluoromethoxycarbonylmethyl group, ethoxycarbonylmethyl group, methoxycarbonylethyl group, ethoxycarbonylethyl group, methoxy group, trifluoro Methoxy group, ethoxy group, n-propoxy group, i-propoxy group, 3,3-dimethyl-n-butoxy group, methylcarbonyloxymethoxy group, ethylcarbonyloxymethoxy group, methylcarbonyloxyethoxy group , Ethylcarbonyloxyethoxy group, methylcarbonylaminomethoxy group, trifluoromethylcarbonylaminomethoxy group, ethylcarbonylaminomethoxy group, methylcarbonylaminoethoxy group, ethylcarbonylaminoethoxy group, methoxy Carbonylmethoxy group, trifluoromethoxycarbonylmethoxy group, ethoxycarbonylmethoxy group, methoxycarbonylethoxy group, ethoxycarbonylethoxy group, methyl amino group, trifluoromethyl amino group, ethyl amino group, n- Propyl amino group, i-propyl amino group, n-butyl amino group, dimethyl amino group, di (trifluoromethyl) amino group, diethyl amino group, di-n-propyl amino group, di-i-propyl amino group, di-n-butyl amino group, methyl Carbonylamino group, trifluoromethylcarbonylamino group, ethylcarbonylamino group, n-propylcarbonylamino group, i-propylcarbonylamino group, n Butylcarbonylamino group, methane sulfone amide group, trifluoromethane sulfone amide group, ethane sulfone amide group, n-propane sulfone amide group, i-propane sulfone amide group, n-butane sulfone amide group, benzene sulfone amide group, p- Toluene sulfone amide group, methylaminocarbonyl group, trifluoromethylaminocarbonyl group, ethylaminocarbonyl group, n-propylaminocarbonyl group, i-propylaminocarbonyl group, n-butylaminocarbonyl group, dimethylaminocarbonyl group, di (trifluoromethyl) aminocarbonyl group, Diethylaminocarbonyl group, di-n-propylaminocarbonyl, di-i-propylaminocarbonyl group, di-c-propylaminocarbonyl group, di-n-butylaminocarbonyl group, methyl (ethyl) aminocarbonyl group, trifluoromethyl (ethyl ) Aminocarbonyl group, methylcarbonyl group, trifluoromethylcarbonyl group, ethyl carbon A carbonyl group, n-propylcarbonyl group, i-propylcarbonyl group, n-butylcarbonyl group, methoxycarbonyl group, trifluoromethoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, i-propoxycarbonyl group, n-butoxycarbonyl group, i-butoxycarbonyl group, s-butoxycarbonyl group, t-butoxycarbonyl group, methanesulfonyl group, trifluoromethanesulfonyl group, ethanesulfonyl group, benzenesulfonyl group, o-biphenylsulfonyl group, m-biphenylsulfonyl group , p-biphenylsulfonyl group, 1-naphthalenesulfonyl group, 2-naphthalenesulfonyl group, phenylcarbonyl group, o-biphenylcarbonyl group, m-biphenylcarbonyl group, p-biphenylcarbonyl group, 1-naphthylcarbonyl group, 2-nap Tylcarbonyl group, hydroxyl group, nitro group, cyano group, formyl group, form amide group, carbamoyl group, sulfo amino group, sulfamoyl group, amino group, and carboxyl group are preferable.

The partial ring structure A in the formulas (11) and (12) is represented by the following formulas (a), (b), formula (c), formula (d), formula (e), formula (f), and formula ( g), formula (h), formula (i), formula (j), formula (k), formula (l), formula (m), formula (n), formula (o), formula (p), formula ( q), formula (r), formula (s), formula (t), formula (u), formula (i), formula (w), formula (x), formula (y), formula (z), formula ( aa), formula (ab), formula (ac), formula (ad), formula (ae), formula (af), formula (ag) and formula (ah)

(Tue 25)

In the case represented by the formula (a), formula (b), formula (c), formula (d), formula (e), formula (f), formula (g), formula (h), formula ( i), Expression (j), Expression (k), Expression (l), Expression (m), Expression (n), Expression (o), Expression (p), Expression (q), Expression (r), Expression ( s), formula (t), formula (u), formula (i), formula (w), formula (x), formula (y), formula (z), formula (aa), formula (ab), formula ( ac), formula (ad), formula (ae), formula (af), formula (ag) and the equation (ah) through each substituent group of ^{R 12, R 13, R 14} , R 15, R 16 and R ¹⁷ do.

First, the formulas (a), (b), (e), (f), (g), (h), (i), (j), (k) and (l) ), Formula (m), formula (n), formula (p), formula (q), formula (ｖ), formula (w), formula (x), formula (ab), formula (ae), formula (af ) And R ¹² and R ¹³ in formula (ag) will be described.

Expression (a), Expression (b), Expression (e), Expression (f), Expression (g), Expression (h), Expression (i), Expression (j), Expression (k), Expression (l), Expression (m), Expression (n), Expression (p), Expression (q), Expression (iii), Expression (w), Expression (x), Expression (ab), Expression (ae), Expression (af) and R ¹² and R ¹³ in the formula (ag) are, each independently, a hydrogen atom, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 - 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom. ), an amino group, a hydroxy group, C _{6 - 14} aryl group, C _{2 - 9} heteroaryl group (wherein the aryl and heteroaryl groups all q of R ¹⁸ (R ¹⁸ represents the same meaning as R ^11, q is from 1 to 3 indicates a integer, in the case of q is 2 or 3, R ¹⁸ may be the same or different) may also optionally be substituted with a), C _{1 -. 6} alkylamino group, a di -C _{1 - 6} alkylaminocarbonyl group , C _{1 -6} alkylcarbonyloxy group, C _{1 -6} alkylcarbonyl group (the alkylcarbonyloxy group and the alkylcarbonyl group is a halogen atom Optionally may be substituted), C _{1 -. 6} alkyl-carbonyl group, C _{3 - 8} cycloalkyl group, a C _{1 - 6} alkoxycarbonyl, C _{1 -6} alkyl sulfonyl group (said cycloalkyl group, an alkoxycarbonyl group and an alkyl alcohol sulfonyl group may be arbitrarily substituted with halogen atom), a carboxyl group, C _{6 -. 14} aryl group (the aryl group may be substituted righteousness being a halogen atom) or a C _{2 -. 9} may be optionally substituted with a heteroaryl group. ), C _{6 - 14} aryl group, C _{2 - 9} heteroaryl group (wherein the aryl and heteroaryl groups all q of R ¹⁸ (R ¹⁸ represents the same meaning as R ^11, q is an integer of 1-3 ., in the case of q is 2 or 3, R ¹⁸ may be the same or different) it may also optionally be substituted with a), C _{1- 6} alkylamino group, a di -C _{1 -. 6} alkylaminocarbonyl group, C _{1 - 6} alkylcarbonyloxy Group, C _{3 -8} cycloalkyl group, C _{1 - 6} alkoxycarbonyl group, C _{1 - 6} alkylsulfonyl, C _{6 - 14} arylsulfonyl group, C _{2 -9} heteroaryl sulfonyl group (the aryl sulfonyl group, and a heteroaryl alcohol The allyl groups are optionally selected from q pieces of R ¹⁸ (R ¹⁸ represents the same meaning as R ¹¹ , q represents an integer of 1 to 3, and when q is 2 or 3, R ¹⁸ may be the same or different.) may be substituted), carboxyl group, C _{6 -14} aryl group or a C _{2 -9} heteroaryl group (the aryl group and heteroaryl group are all q of R ¹⁸ (R ¹⁸ represents the same meaning as R ^11, q Represents an integer of 1 to 3, and when q is 2 or 3, R ¹⁸ may be the same or different.) May be optionally substituted.

Formula (a), Formula (b), Formula (e), Formula (f), Formula (g), Formula (h), Formula (i), Formula (j), Formula (k), Formula (l) , Formula (m), formula (n), formula (p), formula (q), formula ()), formula (w), formula (x), formula (ab), formula (ae), formula (af) And each substituent of R <^12> and R <^13> in a formula (ag) is demonstrated concretely.

The C _{1 - 6} alkyl group as a methyl, trifluoro methyl, ethyl, n- propyl, i- propyl, n- butyl, i- butyl, s- butyl, t- butyl, n- pentyl , 2-pentyl group, 3-pentyl group, i-pentyl group, neopentyl group, 2, 2-dimethyl propyl group, n-hexyl group, 2-hexyl group, 3-hexyl group, 1-methyl-n-pen Tyl group, 1, 1, 2-trimethyl-n-propyl group, 1, 2, 2-trimethyl-n-propyl group, 3, 3- dimethyl- n-butyl group, methylcarbonyloxymethyl group, ethylcarbonyl Oxymethyl group, methylcarbonyloxyethyl group, ethylcarbonyloxyethyl group, methylcarbonylaminomethyl group, trifluoromethylcarbonylaminomethyl group, ethylcarbonylaminomethyl group, methylcarbonylaminoethyl group, ethylcarbonylaminoethyl group, methoxycarbon A carbonylmethyl group, an ethoxycarbonylmethyl group, a methoxycarbonylethyl group, an ethoxycarbonylethyl group, etc. are mentioned,

The C _{6 - 14} aryl group includes, phenyl, o- non penny group, m- non penny group, p- ratio penny group, 1-naphthyl, 2-naphthyl group, 1-anthryl group, 2-anthryl group And 9-anthryl groups, 1-phenanthryl groups, 2-phenanthryl groups, 3-phenanthryl groups, 4-phenanthryl groups, and 9-phenanthryl groups.

The C _{2 - 6} dan be polycyclic heterocyclic group, and constituent atoms _8-9 heteroaryl group include an oxygen atom, a nitrogen atom, a sulfur atom is 1-3 atom C ₂ to the single or 5-7 won can be combined include the ring of ~ to 10 it includes C _{5 -9} condensed polycyclic heterocyclic group 2.

The C ₂ ~ 5 to 7-membered _ring-6 as a monocyclic heterocyclic group, 2-thienyl, 3-thienyl group, 2-frills group, 3-frills group, a 2-pyrazoline group, a 3-pyrazolyl group, 4 Pyranyl group, 1-pyrrolyl group, 2-pyrrolyl group, 3-pyrrolyl group, 1-imidazolyl group, 2-imidazolyl group, 4-imidazolyl group, 1-pyrazoryl group, 3-pyrazoryl group, 4- Pyrazoryl group, 2-thiazolyl group, 4-thiazolyl group, 5-thiazolyl group, 3-isothiazolyl group, 4-isothiazolyl group, 5-isothiazolyl group, 2-oxazoryl group, 4 -Oxazolyl group, 5-oxazolyl group, 3-isoxazaryl group, 4-isooxazoryl group, 5-isooxazoryl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, 2-pyra Genyl group, 2-pyrimidinyl group, 4-pyrimidinyl group, 5-pyrimidinyl group, 3-pyridazinyl group, 4-pyridazinyl group, 2-1, 3, 4-oxazazolyl group , 2-1, 3, 4-thiazoazil group, 3-1, 2, 4-oxazazyl group, 5-1, 2, 4-oxaz Cooker, 3-1, 2, 4-chiaziozyl group, 5-1, 2, 4-chiaziazozyl group, 3-1, 2, 5-oxazazillozyl group and 3-1, 2, 5- Zigzag group, and the like.

Examples of the C _{5 -9} condensed polycyclic heterocycle group of 2 to configure the number of atoms of 8-10, 2-benzofuranyl group, 3-benzofuranyl group, 4-benzofuranyl group, 5-benzofuranyl group, 6-benzofuranyl group, 7-benzofuranyl group, 1-isobenzofuranyl group, 4-isobenzofuranyl group, 5-isobenzofuranyl group, 2-benzothienyl group, 3-benzothienyl group, 4-benzothienyl group, 5-benzothienyl group , 6-benzothienyl group, 7-benzothienyl group, 1-isobenzothienyl group, 4-isobenzothienyl group, 5-isobenzothienyl group, 2-chloromenyl group, 3-chloromenyl group, 4-chlorome Neyl group, 5-Chlomenyl group, 6-Chlomenyl group, 7-Chlomenyl group, 8-Chlomenyl group, 1-Indoridinyl group, 2-Indoridinyl group, 3-Indoridinyl group, 5-Indoridinyl group, 6-indoledinyl group, 7-indoledinyl group, 8-indoledinyl group, 1-isoindolyl group, 2-isoindolyl group, 4-isoindolyl group, 5-isoindolyl group, 1-indolyl group , 2-indole group , 3-indolyl group, 4-indolyl group, 5-indolyl group, 6-indolyl group, 7-indolyl group, 1-indyl group, 2-indole group, 3-indole group, 4-indole group, 5-indazolyl group, 6-indazolyl group, 7-indazolyl group, 1-furinyl group, 2-furinyl group, 3-furinyl group, 6-furinyl group, 7-furinyl group, 8-furinyl group, 2- Quinolyl group, 3-quinolyl group, 4-quinolyl group, 5-quinolyl group, 6-quinolyl group, 7-quinolyl group, 8-quinolyl group, 1-isoquinolyl group, 3-iso Quinolyl group, 4-isoquinolyl group, 5-isoquinolyl group, 6-isoquinolyl group, 7-isoquinolyl group, 8-isoquinolyl group, 1- putadinyl group, 5-putara Dinyl group, 6-putadinyl group, 1-2, 7-naphthyldinyl group, 3-2, 7-naphthyldinyl group, 4-2, 7-naphthyldinyl group, 1-2, 6-naphthyldinyl group, 3-2, 6-naphthyldinyl group, 4-2, 6-naphthyldinyl group, 2-1, 8-naphthyldinyl group, 3-1, 8-naphthyldinyl group, 4-1, 8-naphthyldinyl group, 2-1, 7 -Naphthyldinyl group, 3-1, 7-naphthyldinyl group, 4-1, 7-naphthyldinyl group, 5-1, 7-naphthyldinyl group, 6-1, 7-naphthyldinyl group, 8-1, 7 -Naphthyldinyl group, 2-1, 6-naphthyldinyl group, 3-1, 6-naphthyldinyl group, 4-1, 6-naphthyldinyl group, 5-1, 6-naphthyldinyl group, 7-1, 6 -Naphthyldinyl group, 8-1, 6-naphthyldinyl group, 2-1, 5-naphthyldinyl group, 3-1, 5-naphthyldinyl group, 4-1, 5-naphthyldinyl group, 6-1, 5 -Naphthyldinyl group, 7-1, 5-naphthyldinyl group, 8-1, 5-naphthyldinyl group, 2-quinoxarinyl group, 5-quinoxarinyl group, 6-quinoxarinyl group, 2-quinazolinyl group, 4 -Quinazolinyl group, 5-quinazolinyl group, 6-quinazolinyl group, 7-quinazolinyl group, 8-quinazolinyl group, 3 -cinnolinyl group, 4 -cinnolinyl group, 5 -cinnolinyl group, 6-cin Norinyl group, 7-cinnolinyl group, 8-shinnolinyl group, 2-puteridinyl group, 4-puteridinyl group, 6- puteridinyl group, 7- puteridinyl group, etc. Can.

The C _{1 - 6} Examples of alkylaminocarbonyl group, methylamino group, ethylamino group, n- propylamino group, an i- propylamino group, a butylamino group n-, i- butylamino group, a s- butyl amino group, a t- Butylaminocarbonyl group, 1-pentylaminocarbonyl group, 2-pentylaminocarbonyl group, 3-pentylaminocarbonyl group, i-pentylaminocarbonyl group, neopentylaminocarbonyl, t-pentylaminocarbonyl group, 1-hexylaminocarbonyl group, 2-hexylamino Carbonyl group, 3-hexylaminocarbonyl group, etc. are mentioned,

The di -C _{1 - 6} As the alkylamino group, a dimethylamino group, an ethylamino group if, di -n- propyl aminocarbonyl, di -i- propylamino group, a di -c- propylamino group, a di -n- Butylaminocarbonyl group, di-i-butylaminocarbonyl group, di-s-butylaminocarbonyl group, di-t-butylaminocarbonyl group, di-c-butylaminocarbonyl group, di-1-pentylaminocarbonyl group, di-2-pentylamino Carbonyl group, di-3-pentylaminocarbonyl group, di-i-pentylaminocarbonyl group, dinopentylaminocarbonyl group, di-t-pentylaminocarbonyl group, di-c-pentylaminocarbonyl group, di-hexylaminocarbonyl group, di- 2-hexylaminocarbonyl group, di-hexylaminocarbonyl group, di-C-hexylaminocarbonyl group, di (1-methyl-n-pentyl) aminocarbonyl group, di (1, 1, 2-trimethyl-n-propyl) Ah Nocarbonyl group, di (1, 2, 2-trimethyl-n-propyl) aminocarbonyl group, di (3, 3-dimethyl-n-butyl) aminocarbonyl group, methyl (ethyl) aminocarbonyl group, methyl (n-propyl) ) Aminocarbonyl group, methyl (i-propyl) aminocarbonyl group, methyl (c-propyl) aminocarbonyl group, methyl (n-butyl) aminocarbonyl group, methyl (i-butyl) aminocarbonyl group, methyl (s-butyl) aminocarbonyl group, methyl (t-butyl) aminocarbonyl group, methyl (c-butyl) aminocarbonyl group, ethyl (n-propyl) aminocarbonyl group, ethyl (i-propyl) aminocarbonyl group, ethyl (c-propyl) aminocarbonyl group, ethyl (n-butyl) Aminocarbonyl group, ethyl (i-butyl) aminocarbonyl group, ethyl (s-butyl) aminocarbonyl group, ethyl (t-butyl) aminocarbonyl group, ethyl (c-butyl) aminocarbonyl group, n-propyl (i-propyl) aminocarbonyl group, n-propyl (c -Propyl) aminocarbonyl group, n-propyl (n-butyl) aminocarbonyl group, n-propyl (i-butyl) aminocarbonyl group, n-propyl (s-butyl) aminocarbonyl group, n-propyl (t-butyl) aminocarbonyl group, n-propyl (c-butyl) aminocarbonyl group, i-propyl (c-propyl) aminocarbonyl group, i-propyl (n-butyl) aminocarbonyl group, i-propyl (i-butyl) aminocarbonyl group, i-propyl (s- Butyl) aminocarbonyl group, i-propyl (t-butyl) aminocarbonyl group, i-propyl (c-butyl) aminocarbonyl group, c-propyl (n-butyl) aminocarbonyl group, c-propyl (i-butyl) aminocarbonyl group, c -Propyl (s-butyl) aminocarbonyl group, c-propyl (t-butyl) aminocarbonyl group, c-propyl (c-butyl) aminocarbonyl group, n-butyl (i-butyl) aminocarbonyl group, n-butyl (s-butyl ) Aminocarbonyl group, n-butyl (t-butyl) a Nocarbonyl group, n-butyl (c-butyl) aminocarbonyl group, i-butyl (s-butyl) aminocarbonyl group, i-butyl (t-butyl) aminocarbonyl group, i-butyl (c-butyl) aminocarbonyl group, s-butyl (t-butyl) aminocarbonyl group, s-butyl (c-butyl) aminocarbonyl group, t-butyl (c-butyl) aminocarbonyl group, etc. are mentioned,

The C _{1 - 6} as the alkyl group, methyl group, ethyl group, n- propyl group, i- propyl group, a n- butyl group, i- butyl group, a s- butyl group, a t- butyl group, a 1-pentyl group, 2-pentyl carbonyl group, 3-pentyl carbonyl group, i-pentyl carbonyl group, neopentyl carbonyl group, t-pentyl carbonyl group, 1-hexyl carbonyl group, 2-hexyl carbonyl group, and 3-hexyl carbonyl group are mentioned,

Examples of the C _{3 -8} cycloalkyl group, a c- propyl group, a c- butyl group, 1-methyl -c- propyl group, a 2-methyl -c- propyl group, a c- pentyl group, 1-methyl -c- butyl Carbonyl group, 2-methyl-c-butylcarbonyl group, 3-methyl-c-butylcarbonyl group, 1, 2-dimethyl-c-propylcarbonyl group, 2, 3-dimethyl-c-propylcarbonyl group, 1-ethyl-c-propylcarbonyl group , 2-ethyl-c-propylcarbonyl group, c-hexylcarbonyl group, c-heptylcarbonyl group, c-oakchicarbonyl group, 1-methyl-c-hexylcarbonyl group, 2-methyl-c-hexylcarbonyl group, 3-methyl-c -Hexylcarbonyl group, 1, 2- dimethyl-c-hexylcarbonyl group, 2, 3- dimethyl-c-propylcarbonyl group, 1-ethyl-c-propylcarbonyl group, 1-methyl-c-pentylcarbonyl group, 2-methyl-c- Pentylcarbonyl group, 3-methyl-c-pentylcarbonyl group, 1-ethyl-c-butylcarbonyl , 2-ethyl-c-butylcarbonyl group, 3-ethyl-c-butylcarbonyl group, 1, 2-dimethyl-c-butylcarbonyl group, 1, 3-dimethyl-c-butylcarbonyl group, 2, 2-dimethyl-c-butyl Carbonyl group, 2,3-dimethyl-c-butylcarbonyl group, 2,4-dimethyl-c-butylcarbonyl group, 3,3-dimethyl-c-butylcarbonyl group, 1-n-propyl-c-propylcarbonyl group, 2- n-propyl-c-propylcarbonyl group, 1-i-propyl-c-propylcarbonyl group, 2-i-propyl-c-propylcarbonyl group, 1, 2, 2-trimethyl-c-propylcarbonyl group, 1, 2, 3 -Trimethyl-c-propylcarbonyl group, 2, 2, 3-trimethyl-c-propylcarbonyl group, 1-ethyl-2 -methyl-c-propylcarbonyl group, 2-ethyl-1 -methyl-c-propylcarbonyl group, 2 -Ethyl- 2-methyl-c-propylcarbonyl group, 2-ethyl- 3-methyl-c-propylcarbonyl group, etc. are mentioned,

The C _{1 - 6} As the alkoxycarbonyl group, an ethoxycarbonyl group, ethoxy group, n- propoxy group, i- propoxy group, n- butoxycarbonyl group, i- butoxy group, a s- butoxy group, t- butoxy Carbonyl group, 1-pentyloxycarbonyl group, 2-pentyloxycarbonyl group, 3-pentyloxycarbonyl group, i-pentyloxycarbonyl group, neopentyloxycarbonyl group, t-pentyloxycarbonyl group, 1-hexyloxycarbonyl group, 2-hexyloxycarbonyl group and 3 -Hexyloxycarbonyl group, etc. are mentioned,

The C _{1 - 6} can be mentioned as the alkyl sulfonyl group, sulfonyl group shots, trifluoro methane sulfonyl group and ethane sulfonyl group,

Group C _{6 - 14} arylsulfonyl group As, Zhen sulfonyl group, o- biphenyl sulfonyl group, m--biphenyl sulfonyl group, p- biphenyl sulfonyl group, 1-naphthalene-sulfonyl, naphthalene-2-sulfonyl group, 1-anthracene Sulfonyl group, 2-anthracenesulfonyl group, 9-anthracenesulfonyl group, 1-phenanthrenesulfonyl group, 2-phenanthrenesulfonyl group, 3-phenanthrenesulfonyl group, 4-phenanthrenesulfonyl group, 9-phenanthrenesulfonyl group, etc. Can be mentioned.

The C _{2 - 9} heteroaryl sulfonyl group as, an oxygen atom, a nitrogen atom, a sulfur atom is 1-3 atom C ₂ of 5 - to 7-membered ring which can include, alone or in combination _{- 6} monocyclic clothing sohwansul PO group and configure C ₅ atoms of from 8 to ₁₀ include a group ₉ 2 condensation polycyclic repeat sohwansul sulfonyl.

The C ₂ ~ 5 to 7-membered _ring-6 as a monocyclic clothing fabric sohwansul group, sulfonyl group, 2-thienyl, 3-thienyl sulfonyl group, 2-furyl sulfonyl group, sulfonyl group 3-furyl, 2-pyranyl Sulfonyl group, 3-pyranylsulfonyl group, 4-pyranylsulfonyl group, 1-pyrrolylsulfonyl group, 2-pyrrolylsulfonyl group, 3-pyrrolylsulfonyl group, 1- imidazorylsulfonyl group, 2-imida Zylsulfonyl group, 4-imidazolyl sulfonyl group, 1-pyrazolyl sulfonyl group, 3-pyrazoryl sulfonyl group, 4-pyrazoryl sulfonyl group, 2-thiazolyl sulfonyl group, 4-thiazolyl sulfonyl group, 5-thia Zylsulfonyl group, 3-isothiazolyl sulfonyl group, 4-isothiazolyl sulfonyl group, 5-isothiazolyl sulfonyl group, 2-oxazolyl sulfonyl group, 4-oxazolyl sulfonyl group, 5-oxazolyl sulfonyl group, 3 -Isoxazolylsulfonyl group, 4-isooxazolylsulfonyl group, 5-isooxazolylsulfonyl group, 2-pyridylsulfonyl group, 3-pyridylsulfonyl group, 4-pyridyl Ponyyl group, 2-pyridinylsulfonyl group, 2-pyrimidinylsulfonyl group, 4-pyrimidinylsulfonyl group, 5-pyrimidinylsulfonyl group, 3-pyridazinyl sulfonyl group, 4-pyridazinyl sulfonyl group , 2-1, 3, 4-oxadiazolyl sulfonyl group, 2-1, 3, 4-thiadiazolyl sulfonyl group, 3-1, 2, 4-oxadiazolyl sulfonyl group, 5-1, 2, 4 -Oxia azolyl sulfonyl group, 3-1, 2, 4-thiadiazolyl sulfonyl group, 5-1, 2, 4-thiadiazolyl sulfonyl group, 3-1, 2, 5-oxadiazolyl sulfonyl group, and 3 -1, 2, 5- thiadiazolyl sulfonyl group, etc. are mentioned.

Configuration Examples of the C _{5 -9} condensed polycyclic repeat 2 sohwansul Four groups of atoms up to 8-10, 2-benzofuranyl sulfonyl group, sulfonyl group, 3-benzofuranyl, 4-benzofuranyl sulfonyl group, 5-benzofuranyl Nylsulfonyl group, 6-benzofuranylsulfonyl group, 7-benzofuranylsulfonyl group, 1-isobenzofuranylsulfonyl group, 4-isobenzofuranylsulfonyl group, 5-isobenzofuranylsulfonyl group, 2-benzo Thienylsulfonyl group, 3-benzothienylsulfonyl group, 4-benzothienylsulfonyl group, 5-benzothienylsulfonyl group, 6-benzothienylsulfonyl group, 7-benzothienylsulfonyl group, 1-isobenzothier Neylsulfonyl group, 4-isobenzothienylsulfonyl group, 5-isobenzothienylsulfonyl group, 2-chloromenylsulfonyl group, 3-chloromenylsulfonyl group, 4-chloromenylsulfonyl group, 5-chloromenylsulfonyl group, 6-Chlomenylsulfonyl group, 7-Chlomenylsulfonyl group, 8-Chlomenylsulfonyl group, 1-indoledinylsulfonyl group, 2-indoldinylsulfonyl group, 3- Indolinylsulfonyl group, 5-indoledinylsulfonyl group, 6-indoledinylsulfonyl group, 7-indoledinylsulfonyl group, 8-indoledinylsulfonyl group, 1-isoindolylsulfonyl group, 2-isoindolylsulfonyl group, 4 -Isoindolylsulfonyl group, 5-isoindolylsulfonyl group, 1-indolylsulfonyl group, 2-indolylsulfonyl group, 3-indolylsulfonyl group, 4-indolylsulfonyl group, 5-indolylsulfonyl group, 6-indolylsulfonyl group, 7-indolylsulfonyl group, 1-indazolylsulfonyl group, 2-indazolylsulfonyl group, 3-indazolylsulfonyl group, 4-indazolylsulfonyl group, 5-indazolylsulfonyl group, 6 -Indazolyl sulfonyl group, 7-indazolyl sulfonyl group, 1-furinylsulfonyl group, 2-furinylsulfonyl group, 3-furinylsulfonyl group, 6-furinylsulfonyl group, 7-furinylsulfonyl group, 8- Furinylsulfonyl group, 2-quinolylsulfonyl group, 3-quinolylsulfonyl group, 4-quinolylsulfonyl group, 5-quinolylsulfonyl group, 6-quinolylsulfonyl group, 7-quinolylsulfonyl group, 8-quinolylsulfonyl group, 1-isoquinolylsulfonyl group, 3-isoquinolylsulfonyl group, 4-isoquinolylsulfonyl group, 5-isoquinolylsulfonyl group, 6-isoquinolylsulfonyl group, 7-iso Quinolylsulfonyl group, 8-isoquinolylsulfonyl group, 1-putadinylsulfonyl group, 5-putadinylsulfonyl group, 6-putadinylsulfonyl group, 1-2, 7-naphthyldinylsulfonyl group, 3 -2, 7-naphthyldinylsulfonyl group, 4-2, 7-naphthyldinylsulfonyl group, 1-2, 6-naphthyldinylsulfonyl group, 3-2, 6-naphthyldinylsulfonyl group, 4-2 , 6-naphthyldinylsulfonyl group, 2-1, 8-naphthyldinylsulfonyl group, 3-1, 8-naphthyldinylsulfonyl group, 4-1, 8-naphthyldinylsulfonyl group, 2-1, 7 -Naphthyldinylsulfonyl group, 3-1, 7-naphthyldinylsulfonyl group, 4-1, 7-naphthyldinylsulfonyl group, 5-1, 7-naphthyldinylsulfonyl group, 6-1, 7-naph Tildinylsulfonyl group, 8-1, 7-naphthyldinylsulfonyl group, 2-1, 6-naphthyldinylsulfonyl group, 3 -1, 6-naphthyldinylsulfonyl group, 4-1, 6-naphthyldinylsulfonyl group, 5-1, 6-naphthyldinylsulfonyl group, 7-1, 6-naphthyldinylsulfonyl group, 8-1 , 6-naphthyldinylsulfonyl group, 2-1, 5-naphthyldinylsulfonyl group, 3-1, 5-naphthyldinylsulfonyl group, 4-1, 5-naphthyldinylsulfonyl group, 6-1, 5 -Naphthyldinylsulfonyl group, 7-1, 5-naphthyldinylsulfonyl group, 8-1, 5-naphthyldinylsulfonyl group, 2-quinoxalinylsulfonyl group, 5-quinoxalinylsulfonyl group, 6-quinox Salinylsulfonyl group, 2-quinazolinylsulfonyl group, 4-quinazolinylsulfonyl group, 5-quinazolinylsulfonyl group, 6-quinazolinylsulfonyl group, 7-quinazolinylsulfonyl group, 8-quinazolinyl Sulfonyl group, 3-cinnolinylsulfonyl group, 4-cinnolinylsulfonyl group, 5-cinnolinylsulfonyl group, 6-cinnolinylsulfonyl group, 7-cinnolinylsulfonyl group, 8-cinnolinylsulfonyl group , 2- putridinylsulfonyl group, 4- putridinylsulfonyl group, 6- puteridi And the like sulfonyl group and 7-Puteri pyridinyl sulfonyl group.

The C _{6 - 14} aryl group as phenyl group, biphenyl group o-, m- biphenyl group, p- biphenyl group, a 1-naphthyl group, a 2-naphthyl group, 1-tree do not le group, 2 -Anthryl carbonyl group, 9- anthryl carbonyl group, 1-phenan tricarbonyl group, 2-phenan tricarbonyl group, 3-phenan tricarbonyl group, 4-phenan tricarbonyl group, 9-phenan tricarbonyl group, etc. are mentioned. Can be.

Examples of the C _{2 -9} heteroaryl group, an oxygen atom, a nitrogen atom, a sulfur atom is 1 to 3 atoms of the C ₂ to single or 5-7 won which can be combined include the _ring-number of ₆ monocyclic heterocyclic group, and constituent atoms of from 8 to 10 include a C _{5 -9} condensed heterocyclic 2 cyclic group.

C ₂ of the 5 to 7-membered _ring-6 As recalled monocyclic clothing group, a 2-thienyl group, a 3-thienyl group, a 2-furyl group, a 3-furyl group, a 2-pyranyl group, 3-pyrazolyl Nylcarbonyl group, 4-pyranylcarbonyl group, 1-pyrrolylcarbonyl group, 2-pyrrolylcarbonyl group, 3-pyrrolylcarbonyl group, 1-imidazoylcarbonyl group, 2-imidazolyl carbonyl group, 4-imidazoyl carbonyl group, 1- Pyrazoryl carbonyl group, 3-pyrazoryl carbonyl group, 4-pyrazoryl carbonyl group, 2-thiazoyl carbonyl group, 4-thiazolyl carbonyl group, 5-thiazolyl carbonyl group, 3-isothiazolyl carbonyl group, 4-isothiazolyl carbonyl group, 5- Isothiazolyl carbonyl group, 2-oxazolyl carbonyl group, 4-oxazolyl carbonyl group, 5-oxazolyl carbonyl group, 3-isoxazolyl carbonyl group, 4-isooxazoryl carbonyl group, 5-isoxozazo Carbonyl group, 2-pyridylcarbonyl group, 3-pyridylcarbonyl group, 4-pyridylcarbonyl group, 2-pyridinylcarbonyl group, 2-pyrimidinylcarbonyl group, 4-pyrimidinylcarbonyl group, 5-pyrimidinylcarbonyl group, 3- Pyridazinyl carbonyl group, 4-pyridazinyl carbonyl group, 2-1, 3, 4-oxadiazolyl carbonyl group, 2-1, 3, 4-thiadiazolyl carbonyl group, 3-1, 2, 4-oxadiazolyl carbonyl group , 5-1, 2, 4-oxadiazolyl carbonyl group, 3-1, 2, 4-thiadiazolyl carbonyl group, 5-1, 2, 4-thiadiazolyl carbonyl group, 3-1, 2, 5-oxadia Zyl carbonyl group, 3-1, 2, 5- thiadiazolyl carbonyl group, etc. are mentioned.

Examples of the C _{5 -9} condensed polycyclic heterocyclic group of 2 to configure the number of 8 to 10 atoms, 2-benzofuranyl group, 3-benzofuranyl group, 4-benzofuranyl group, 5-benzofuranyl group, 6 -Benzofuranylcarbonyl group, 7-benzofuranylcarbonyl group, 1-isobenzofuranylcarbonyl group, 4-isobenzofuranylcarbonyl group, 5-isobenzofuranylcarbonyl group, 2-benzothienylcarbonyl group, 3-benzothienylcarbonyl group , 4-benzothienylcarbonyl group, 5-benzothienylcarbonyl group, 6-benzothienylcarbonyl group, 7-benzothienylcarbonyl group, 1-isobenzothienylcarbonyl group, 4-isobenzothienylcarbonyl group, 5-isobenzothiene Nylcarbonyl group, 2-Chlomenylcarbonyl group, 3-Chlomenylcarbonyl group, 4-Chlomenyl carbonyl group, 5-Chlomenyl carbonyl group, 6-Chlomenyl carbonyl group, 7-Chlomenyl carbonyl group, 8-Chlomenyl carbon A carbonyl group, 1-indoledinylcarbonyl group, 2-indoledinylcarbonyl group, 3-indoledinylcarbonyl group, 5-indoledinylcarbonyl group, 6-indoledinylcarbonyl group, 7-indoledinylcarbonyl group, 8-indoledinylcarbonyl group, 1-isoiso Indolylcarbonyl group, 2-isoindolylcarbonyl group, 4-isoindolylcarbonyl group, 5-isoindolylcarbonyl group, 1-indolylcarbonyl group, 2-indolylcarbonyl group, 3-indolylcarbonyl group, 4-indolylcarbonyl group, 5 -Indolyl carbonyl group, 6- indolyl carbonyl group, 7- indolyl carbonyl group, 1- indazolyl carbonyl group, 2- indazolyl carbonyl group, 3- indazolyl carbonyl group, 4- indazolyl carbonyl group, 5- indazolyl carbonyl group, 6- ind Zolylcarbonyl group, 7-indazolylcarbonyl group, 1-furinylcarbonyl group, 2-furinylcarbonyl group, 3-furinylcarbonyl group, 6-furinylcarbonyl group, 7-furinylcarbonyl group, 8-furinylcarbon Bonyl group, 2-quinolylcarbonyl group, 3-quinolylcarbonyl group, 4-quinolylcarbonyl group, 5-quinolylcarbonyl group, 6-quinolylcarbonyl group, 7-quinolylcarbonyl group, 8-quinolylcarbonyl group, 1-isoquinolyl Carbonyl group, 3-isoquinolylcarbonyl group, 4-isoquinolylcarbonyl group, 5-isoquinolylcarbonyl group, 6-isoquinolylcarbonyl group, 7-isoquinolylcarbonyl group, 8-isoquinolylcarbonyl group, 1-putaradinylcarbonyl group , 5-futaradinylcarbonyl group, 6-futaradinylcarbonyl group, 1-2, 7-naphthyldinylcarbonyl group, 3-2, 7-naphthyldinylcarbonyl group, 4-2, 7-naphthyldinylcarbonyl group, 1- 2, 6-naphthyldinylcarbonyl group, 3-2, 6-naphthyldinylcarbonyl group, 4-2, 6-naphthyldinylcarbonyl group, 2-1, 8-naphthyldinylcarbonyl group, 3-1, 8-naphthyl Dynylcarbonyl group, 4-1, 8-naphthyldinylcarbonyl group, 2-1, 7-naphthyldinylcar Bonyl group, 3-1, 7-naphthyldinylcarbonyl group, 4-1, 7-naphthyldinylcarbonyl group, 5-1, 7-naphthyldinylcarbonyl group, 6-1, 7-naphthyldinylcarbonyl group, 8-1 , 7-naphthyldinylcarbonyl group, 2-1, 6-naphthyldinylcarbonyl group, 3-1, 6-naphthyldinylcarbonyl group, 4-1, 6-naphthyldinylcarbonyl group, 5-1, 6-naphthyldinyl Carbonyl group, 7-1, 6-naphthyldinylcarbonyl group, 8-1, 6-naphthyldinylcarbonyl group, 2-1, 5-naphthyldinylcarbonyl group, 3-1, 5-naphthyldinylcarbonyl group, 4-1, 5-naphthyldinylcarbonyl group, 6-1, 5-naphthyldinylcarbonyl group, 7-1, 5-naphthyldinylcarbonyl group, 8-1, 5-naphthyldinylcarbonyl group, 2-quinoxalinylcarbonyl group, 5-quinox Salinylcarbonyl group, 6-quinoxalinylcarbonyl group, 2-quinazolinylcarbonyl group, 4-quinazolinylcarbonyl group, 5-quinazolinylcarbonyl group, 6-quinazolinylcarbonyl group, 7- Nazolinylcarbonyl group, 8-quinazolinylcarbonyl group, 3-cinnolinylcarbonyl group, 4-cinnolinylcarbonyl group, 5-cinnolinylcarbonyl group, 6-cinnolinylcarbonyl group, 7-cinnolinylcarbonyl group, 8-cin A norinyl carbonyl group, a 2- putridinyl carbonyl group, 4- putridinyl carbonyl group, a 6- putridinyl carbonyl group, a 7- putridinyl carbonyl group, etc. are mentioned.

Expression (a), Expression (b), Expression (e), Expression (f), Expression (g), Expression (h), Expression (i), Expression (j), Expression (k), Expression (l), Expression (m), Expression (n), Expression (p), Expression (q), Expression (iii), Expression (w), Expression (x), Expression (ab), Expression (ae), Expression (af) and R ¹² and R ¹³ in formula (ag) are

Independently, a hydrogen atom, a methyl group, an ethyl group, n-propyl group, i-propyl group, n-butyl group, n-pentyl group, i-pentyl group, methylcarbonyloxymethyl group, ethylcarbonyloxymethyl group, and methyl carbon Carbonyloxyethyl group, ethylcarbonyloxyethyl group, methylcarbonylaminomethyl group, ethylcarbonylaminoethyl group, methylcarbonylaminoethyl group, ethylcarbonylaminoethyl group, methoxycarbonylmethyl group, ethoxycarbonylmethyl group, methoxycarbonyl Ethyl group, ethoxycarbonylethyl group, phenyl group, o-biphenylyl group, m-biphenylyl group, p-biphenylyl group, 1-naphthyl group, 2-naphthyl group,, 2-pyridyl group, 3-pyridyl group, 4 -Pyridyl group, methylaminocarbonyl group, ethylaminocarbonyl group, n-propylaminocarbonyl group, i-propylaminocarbonyl group, n-butylaminocarbonyl group, dimethylaminocarbonyl group, giethylaminocarbonyl group, di-n-propylami Nocarbonyl group, di-i-propylaminocarbonyl group, di-c-propylaminocarbonyl group, di-n-butylaminocarbonyl group, methylcarbonyl group, ethylcarbonyl group, n-propylcarbonyl group, i-propylcarbonyl group, n-butylcarbonyl group, c- Pentylcarbonyl group, c-hexylcarbonyl group, methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, i-propoxycarbonyl group, n-butoxycarbonyl group, i-butoxycarbonyl group, s-butoxycarbonyl group, t-butoxy Carbonyl group, methanesulfonyl group, trifluoromethanesulfonyl group, benzenesulfonyl group, o-biphenylsulfonyl group, m-biphenylsulfonyl group, p-biphenylsulfonyl group, 1-naphthalenesulfonyl group, 2-naphthalenesulfonyl group, 2 -Pyridylsulfonyl group, 3-pyridylsulfonyl group, 4-pyridylsulfonyl group, phenylcarbonyl group, o-biphenylcarbonyl group, m-biphenylcarbonyl group, p-biphenylcarbonyl group, 1-naphthylca A carbonyl group, 2-naphthylcarbonyl group, 2-pyridylcarbonyl group, 3-pyridylcarbonyl group, and 4-pyridylcarbonyl group are preferable. More preferably, they are a hydrogen atom and a methyl group.

Next, the formula (a), formula (b), formula (c), formula (d), formula (f), formula (g), formula (h), formula (j), formula (k), and formula ( m), formula (n), formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (ｖ), formula ( w), formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae) and R ¹⁴ , R ¹⁵ , R in formula (af) ¹⁶ and R ¹⁷ are described. Expression (a), Expression (b), Expression (c), Expression (d), Expression (f), Expression (g), Expression (h), Expression (j), Expression (k), Expression (m), Expression (n), Expression (o), Expression (p), Expression (q), Expression (r), Expression (s), Expression (t), Expression (u), Expression (i), Expression (w), R ¹⁴ , R ¹⁵ , R ¹⁶ and R in formulas (y), (z), (aa), (ab), (ac), (ad), (ae) and (af) ¹⁷ is,

Each independently represent a hydrogen atom, a halogen atom, a C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 -. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), amino group, hydroxy group, C _{6 - 14} aryl group, C _{2 - 9} heteroaryl group (wherein the aryl and heteroaryl groups all r of r ¹⁹ (r ¹⁹ represents the same meaning as r ^11, r is optionally substituted by the same meanings as q). may be), C _{1 -. 6} alkylamino group, a di -C _{1 - 6} alkylaminocarbonyl group, C _{1 - 6} alkylcarbonyloxy group, C _{1 -6} alkylcarbonyl group (the alkylcarbonyloxy group and the alkylcarbonyl group are may be optionally substituted with a halogen atom), C _{1 -. 6} alkyl-carbonyl group, C _{3 - 8} cycloalkyl group, a C _{1 - 6} alkoxycarbonyl, C _{1 -6} alkyl sulfonyl group (said cycloalkyl group, an alkoxycarbonyl group And the alkylsulfonyl group may be arbitrarily substituted with halogen atom), a carboxyl group, C _{6 -14} aryl group (the aryl group may be arbitrarily substituted with halogen atom) or a C _{2 -.. 9} heteroaryl group optionally may be substituted by there), C _{3 - 8} cycloalkyl group (the alkyl group hash claw may be arbitrarily substituted with halogen atom, C _{1 -6} alkoxy group (said alkoxy group is a halogen atom), and optionally may be substituted with amino group or hydroxyl group). C _{1 -6} alkoxy group (said alkoxy group, a halogen atom, C _{1 -. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), a carboxyl group, an amino group, a hydroxy group, C _{6 - 14} aryl group or C _{2 - 9} heteroaryl group (the aryl group and heteroaryl group are both r ¹⁹ (R ¹⁹ represents the same meaning as R ¹¹ , r represents the same meaning as q). . It may also optionally be substituted) may also optionally be substituted with a), C _{1 -. 6} thioalkoxy group (the thioalkoxy group, a halogen atom, C _{1 -6} alkoxy group (said alkoxy group may be substituted with a halogen atom, optionally there), a carboxyl group, a hydroxy group, C _{6 - 14} aryl group or C _{2 - 9} heteroaryl group (wherein the aryl and heteroaryl groups all r of r ¹⁹ (r ¹⁹ represents the same meaning as r ^11, r is q . with the same meaning) may also optionally be substituted by a) may also optionally be substituted by a) hydroxyl group, C _{6 -. 14} aryl group, C _{2 - 9} heteroaryl group (the aryl group and heteroaryl group either r of r ¹⁹ (. r ¹⁹ represents the same meaning as r ^11, r has the same meaning as q) it may also optionally be substituted with a), C _{1 -. 6} alkylcarbonyloxy group, a nitro Group, cyano group, formyl group, formamide group, An amino group, a sulfo, C _{1 - 6} alkylamino group, a di -C _{1 - 6} alkyl group, a C _{6 - 14} aryl group, a C _{2 - 9} heteroaryl group (all of said aryl group and heteroaryl group have two r R ¹⁹ ( . R ¹⁹ represents the same meaning as R ^11, r represents a mean the same as q) may also optionally be substituted with a), C _{1 -. 6} alkylcarbonyl group, C _{1 - 6} alkyl sulfonamide group, carbamoyl, C _{1 - 6} alkylamino group, a di -C _{1 - 6} alkylaminocarbonyl group, C _{1 - 6} alkylcarbonyl group, C _{6 - 14} aryl group, a C _{2 -9} heteroaryl group (the aryl group and heteroaryl group are both r of r ¹⁹ (. r ¹⁹ represents the same meaning as r ^11, r has the same meaning as q) may also optionally be substituted with a), C _{1 -. 6} alkoxycarbonyl group, a sulfamoyl group, C _{1 - 6} alkylsulfonyl , C _{6 - 14} arylsulfonyl group, C _{2 -9} heteroaryl sulfonyl group (the aryl sulfonyl and heteroaryl-sulfonyl group of all r R ¹⁹ (R ¹⁹ represents the same meaning as R ^11, q and r are the same stands for the meaning) may also optionally be substituted with a) carboxyl group or a C _{2 -. 9} heterocyclic group krill

(The heterocyclic group is methacrylic, halogen atoms, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{-. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), optionally substituted with an amino group, a carboxyl group or a hydroxyl group may be), C _{1 -. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), C _{6 -. 14} aryl group, C _{2 - 9} heteroaryl group (wherein the aryl and heteroaryl groups all r May be optionally substituted by R ¹⁹ (R ¹⁹ has the same meaning as R ¹¹ and r has the same meaning as q).), A hydroxyl group, a nitro group, a cyano group, a formyl group, a formamide group, an amino group, a C _{- 6} alkylamino group, a di -C _{1 - 6} alkyl group, C _{1 - 6} alkylcarbonyl group, C _{1 - 6} alkyl sulfonamide group, a carbamoyl group, C _{1 - 6} alkylamino group, a di -C _{1 - 6} alkylaminocarbonyl group, C _{1 - 6} alkylcarbonyl group, C _{1 - 6} alkoxycarbonyl group, a sulfamoyl group, C _{1 -. 6} may be optionally substituted with an alkylsulfonyl group, a carboxyl group or C _{6 -14} aryl group) shows a.

Expression (a), Expression (b), Expression (c), Expression (d), Expression (f), Expression (g), Expression (h), Expression (j), Expression (k), Expression (m), Expression (n), Expression (o), Expression (p), Expression (q), Expression (r), Expression (s), Expression (t), Expression (u), Expression (i), Expression (w), R ¹⁴ , R ¹⁵ , R ¹⁶ and R in formulas (y), (z), (aa), (ab), (ac), (ad), (ae) and (af) Each atom of ¹⁷ and each substituent are demonstrated concretely. Examples of the halogen atom, and a fluorine atom, a chlorine atom, a bromine atom and an oxo atom, and the C _{1 - 6} alkyl group as methyl, ethyl, n- propyl, i- propyl, n- butyl, i- Butyl group, s-butyl group, t-butyl group, n-pentyl group, 2-pentyl group, 3-pentyl group, i-pentyl group, neopentyl group, 2, 2-dimethyl propyl group, n-hexyl group, 2-hexyl group, 3-hexyl group, 1-methyl-n-pentyl group, 1, 1, 2-trimethyl-n-propyl group, 1, 2, 2-trimethyl-n-propyl group, and 3, 3 -Dimethyl-n-butyl group, methylcarbonyloxymethyl group, ethylcarbonyloxymethyl group, methylcarbonyloxyethyl group, ethylcarbonyloxyethyl group, methylcarbonylaminomethyl group, ethylcarbonylaminomethyl group, methylcarbonylaminoethyl group, Ethylcarbonylaminoethyl group, methoxycarbonylmethyl group, ethoxycarbonylmethyl group, methoxycarbonylethyl group, ethoxycarbonylethyl group, etc. Can, and

C _{3 - 8} cycloalkyl group as, c- propyl, c- butyl, 1-methyl -c- propyl, 2-methyl -c- propyl, c- pentyl, 1-methyl -c- butyl, 2-methyl -c- Butyl, 3-methyl-c-butyl, 1,2-dimethyl-c-propyl, 2,3-dimethyl-c-propyl, 1-ethyl-c-propyl, 2-ethyl-c-propyl, c-hexyl, c-heptyl, c-octyl, 1-methyl-c-hexyl, 2-methyl-c-hexyl, 3-methyl-c-hexyl, 1,2-dimethyl-c-hexyl, 2,3-dimethyl-c- Propyl, 1-ethyl-c-propyl, 1-methyl-c-pentyl, 2-methyl-c-pentyl, 3-methyl-c-pentyl, 1-ethyl-c-butyl, 2-ethyl-c-butyl, 3-ethyl-c-butyl, 1,2-dimethyl-c-butyl, 1,3-dimethyl-c-butyl, 2,2-dimethyl-c-butyl, 2,3-dimethyl-c-butyl, 2, 4-dimethyl-c-butyl, 3,3-dimethyl-c-butyl, 1-n-propyl-c-propyl, 2-n-propyl-c-propyl, 1-i-propyl-c-propyl, 2- i-propyl-c-propyl, 1,2,2-trimethyl-c-propyl, 1,2,3-trimethyl-c-propyl, 2,2,3-trimethyl-c-propyl, 1-ethyl 2-methyl-c-propyl, 2-ethyl-1-methyl-c-propyl, 2-ethyl-2-methyl-c-propyl and 2-ethyl-3-methyl-c-propyl And,

The C _{1 - 6} alkoxy group includes a methoxy group, an ethoxy group, n- propoxy, i- propoxy, n- butoxy, i- butoxy, s- butoxy group, t- butoxy group, 1-pentyl Oxy group, 2-pentyl oxy group, 3-pentyl oxy, i-pentyl oxy, neopentyl oxy, 2, 2- dimethyl propoxy, 1-hexyl oxy, 2-hexyl oxy group, 3-hexyl oxy group, 1- Methyl-n-pentyl oxy, 1, 1, 2-trimethyl-n-propoxy, 1, 2, 2-trimethyl-n-propoxy and 3, 3-dimethyl-n-butoxy groups You can

C _{1 - 6} alkoxy group includes, methylthio, ethylthio, n- propyl thio, i- propyl thio, alkylthio c- propyl, n- butylthio, i- butylthio, butylthio s-, t- butylthio, n-pentyl thio, i-pentyl thio, neopentyl thio, t-pentyl thio, n-hexyl thio and c-hexyl thio;

The C _{6 - 14} aryl group includes, phenyl, o- non penny group, m- non penny group, p- ratio penny group, 1-naphthyl, 2-naphthyl group, 1-anthryl group, 2-anthryl group And 9-anthryl groups, 1-phenanthryl groups, 2-phenanthryl groups, 3-phenanthryl groups, 4-phenanthryl groups, and 9-phenanthryl groups.

The C _{2 - 6} dan be polycyclic heterocyclic group, and constituent atoms _8-9 heteroaryl group include an oxygen atom, a nitrogen atom, a sulfur atom is 1-3 atom C ₂ to the single or 5-7 won which can be combined include the ring a C ₅ - to 10 _- includes the ₉ condensed polycyclic heterocyclic group 2.

The C ₂ ~ 5 to 7-membered _ring-6 as a monocyclic heterocyclic group, 2-thienyl, 3-thienyl group, 2-frills group, 3-frills group, a 2-pyrazoline group, a 3-pyrazolyl group, 4 Pyranyl group, 1-pyrrolyl group, 2-pyrrolyl group, 3-pyrrolyl group, 1-imidazolyl group, 2-imidazolyl group, 4-imidazolyl group, 1-pyrazoryl group, 3-pyrazoryl group, 4- Pyrazoryl group, 2-thiazolyl group, 4-thiazolyl group, 5-thiazolyl group, 3-isothiazolyl group, 4-isothiazolyl group, 5-isothiazolyl group, 2-oxazoryl group, 4 -Oxazolyl group, 5-oxazolyl group, 3-isoxazaryl group, 4-isooxazoryl group, 5-isooxazoryl group, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, 2-pyra Genyl group, 2-pyrimidinyl group, 4-pyrimidinyl group, 5-pyrimidinyl group, 3-pyridazinyl group, 4-pyridazinyl group, 2-1, 3, 4-oxadiazolyl group, 2- 1, 3, 4-thiadiazolyl group, 3-1, 2, 4-ox saradiazolyl group, 5-1, 2, 4-oxadi Cooking group, 3-1, 2, 4-thiadiazolyl group, 5-1, 2, 4-thiadiazolyl group, 3-1, 2, 5-oxadiazolyl group and 3-1, 2, 5- And a thiadiazolyl group.

The configuration of the C ₅ atomic number of from 8 to _{10 9} as the condensed tricyclic heterocyclic group 2, 2-benzofuranyl group, 3-benzofuranyl group, 4-benzofuranyl group, 5-benzofuranyl group, 6-benzofuranyl group, 7-benzofuranyl group, 1-isobenzofuranyl group, 4-isobenzofuranyl group, 5-isobenzofuranyl group, 2-benzothienyl group, 3-benzothienyl group, 4-benzothienyl group, 5-benzothienyl group , 6-benzothienyl group, 7-benzothienyl group, 1-isobenzothienyl group, 4-isobenzothienyl group, 5-isobenzothienyl group, 2-chloromenyl group, 3-chloromenyl group, 4-chlorome Neyl group, 5-Chlomenyl group, 6-Chlomenyl group, 7-Chlomenyl group, 8-Chlomenyl group, 1-Indoridinyl group, 2-Indoridinyl group, 3-Indoridinyl group, 5-Indoridinyl group, 6-indoledinyl group, 7-indoledinyl group, 8-indoledinyl group, 1-isoindolyl group, 2-isoindolyl group, 4-isoindolyl group, 5-isoindolyl group, 1-indolyl group , 2-indoleyl , 3-indolyl group, 4-indolyl group, 5-indolyl group, 6-indolyl group, 7-indolyl group, 1-indyl group, 2-indole group, 3-indole group, 4-indole group, 5-indazolyl group, 6-indazolyl group, 7-indazolyl group, 1-furinyl group, 2-furinyl group, 3-furinyl group, 6-furinyl group, 7-furinyl group, 8-furinyl group, 2- Quinolyl group, 3-quinolyl group, 4-quinolyl group, 5-quinolyl group, 6-quinolyl group, 7-quinolyl group, 8-quinolyl group, 1-isoquinolyl group, 3-iso Quinolyl group, 4-isoquinolyl group, 5-isoquinolyl group, 6-isoquinolyl group, 7-isoquinolyl group, 8-isoquinolyl group, 1- putadinyl group, 5-putara Dinyl group, 6-putaradinyl group, 1-2, 7-naphthyldinyl group, 3-2, 7-naphthyldinyl group, 4-2, 7-naphthyldinyl group, 1-2, 6-naphthyldinyl group, 3-2, 6-naphthyldinyl group, 4-2, 6-naphthyldinyl group, 2-1, 8-naphthyldinyl group, 3-1, 8-naphthyldinyl group, 4-1, 8-naphthyldinyl group, 2-1, 7-naphthyldinyl group, 3-1, 7-naphthyldinyl group, 4-1, 7-naphthyldinyl group, 5-1, 7-naphthyldinyl group, 6-1, 7-naphthyldinyl group, 8-1, 7-naphthyldinyl group, 2-1, 6-naphthyldinyl group, 3-1, 6-naphthyldinyl group, 4-1, 6-naphthyldinyl group, 5-1, 6-naphthyldinyl group, 7-1, 6-naphthyldinyl group, 8-1, 6-naphthyldinyl group, 2-1, 5-naphthyldinyl group, 3-1, 5-naphthyldinyl group, 4-1, 5-naphthyldinyl group, 6-1, 5-naphthyldinyl group, 7-1, 5-naphthyldinyl group, 8-1, 5-naphthyldinyl group, 2-quinoxarinyl group, 5-quinoxarinyl group, 6-quinoxarinyl group, 2-quinazolinyl group, 4-quinazolinyl group, 5-quinazolinyl group, 6-quinazolinyl group, 7-quinazolinyl group, 8-quinazolinyl group, 3-shinnolinyl group, 4-shinnolinyl group, 5-shinnolinyl group, 6- Cinnolinyl group, 7-cinnolinyl group, 8-shinnolinyl group, 2-puteridinyl group, 4-puteridinyl group, 6- puteridinyl group, 7- puteridinyl group, etc. Can.

The C _{1 - 6} alkylcarbonyloxy As the group, methyl carbonyloxy group, ethyl carbonyloxy group, n- propyl carbonyloxy group, i- propyl carbonyloxy group, n- butyl carbonyloxy group, i- Butylcarbonyloxy group, s-butylcarbonyloxy group, t-butylcarbonyloxy group, 1-pentyl carbonyloxy group, 2-pentyl carbonyloxy group, 3-pentyl carbonyloxy group, i-pentyl carbon Carbonyloxy group, neopentylcarbonyloxy group, t-pentylcarbonyloxy group, 1-hexyl carbonyloxy group, 2-hexyl carbonyloxy group, 3-hexyl carbonyloxy group, 1-methyl-n-pentyl Carbonyloxy group, 1, 1, 2-trimethyl-n-propylcarbonyloxy group, 1, 2, 2-trimethyl-n-propylcarbonyloxy group, and 3, 3- dimethyl-n-butylcarbono And a silyloxy group,

The C _{1 - 6} alkyl as an amino group, methylamino group, ethylamino group, n- propylamino group, i- propyl group, a c- propyl group, a n- butyl group, i- butyl group, a s- butyl group, a t- butyl group, c-butyl amino group, 1-pentyl amino group, 2-pentyl amino group, 3-pentyl amino group, i-pentyl amino group, neopentyl amino group, t-pentyl amino group, c-pentyl amino group, 1-hexyl amino group, 2-hexyl amino group, 3 -Hexyl amino group, c-hexyl amino group, 1-methyl-n-pentyl amino group, 1, 1, 2-trimethyl-n-propyl amino group, 1, 2, 2-trimethyl-n-propyl amino group, and 3, 3- Dimethyl-n-butyl amino group etc. are mentioned,

The di -C _{1 - 6} alkyl as an amino group, dimethylamino group, diethylamino group, di -n- propyl group, a di--i- propyl group, a di--c- propylamino group, di -n- butyl group, a di--i- Butyl amino group, di-s-butyl amino group, di-t-butyl amino group, di-c-butyl amino group, di-1 pentyl amino group, di-2 pentyl amino group, di-3 pentyl amino group, di-i-pentyl Amino group, EL neopentylamino group, di-t-pentyl amino group, di-c-pentyl amino group, di-1 hexyl amino group, di-2-hexyl amino group, di-3 hexyl amino group, di-c-hexyl amino group, di (1-methyl-n-pentyl) amino group, di (1, 1, 2-trimethyl-n-propyl) amino group, di (1, 2, 2-trimethyl-n-propyl) amino group, di (3, 3 -Dimethyl-n-butyl) amino group, methyl (ethyl) amino group, methyl (n-propyl) amino group, methyl (i-propyl) amino group, methyl (c-propyl) amino group, Tyl (n-butyl) amino group, methyl (i-butyl) amino group, methyl (s-butyl) amino group, methyl (t-butyl) amino group, methyl (c-butyl) amino group, ethyl (n-propyl) amino group, ethyl ( i-propyl) amino group, ethyl (c-propyl) amino group, ethyl (n-butyl) amino group, ethyl (i-butyl) amino group, ethyl (s-butyl) amino group, ethyl (t-butyl) amino group, ethyl (c- Butyl) amino group, n-propyl (i-propyl) amino group, n-propyl (c-propyl) amino group, n-propyl (n-butyl) amino group, n-propyl (i-butyl) amino group, n-propyl (s- Butyl) amino group, n-propyl (t-butyl) amino group, n-propyl (c-butyl) amino group, i-propyl (c-propyl) amino group, i-propyl (n-butyl) amino group, i-propyl (i- Butyl) amino group, i-propyl (s-butyl) amino group, i-propyl (t-butyl) amino group, i-propyl (c-butyl) amino group, c-propyl (n-butyl) amino , c-propyl (i-butyl) amino group, c-propyl (s-butyl) amino group, c-propyl (t-butyl) amino group, c-propyl (c-butyl) amino group, n-butyl (i-butyl) amino group , n-butyl (s-butyl) amino group, n-butyl (t-butyl) amino group, n-butyl (c-butyl) amino group, i-butyl (s-butyl) amino group, i-butyl (t-butyl) amino group , i-butyl (c-butyl) amino group, s-butyl (t-butyl) amino group, s-butyl (c-butyl) amino group and t-butyl (c-butyl) amino group, etc. may be mentioned,

The C _{6 -14} aryl group as phenyl group, biphenyl group o-, m- biphenyl group, p- biphenyl group, a 1-naphthyl group, a 2-naphthyl group, 1-amino group not ornaments, 2 Inner undecorated amino group, 9-undecorated amino group, 1-phenanthryl amino group, 2-phenanthryl amino group, 3-phenanthryl amino group, 4-phenanthryl amino group, and 9-phenanthryl amino group are mentioned

Examples of the C _{2 -9} heteroaryl group, an oxygen atom, a nitrogen atom, a sulfur atom is 1 to 3 atoms of the C ₂ to single or 5-7 won which can be combined include the _ring-number of ₆ monocyclic heterocyclic group, and constituent atoms of up to 8 to 10 containing the condensed C _{5 -9} 2 cyclic heterocyclic amino group.

5-7 wherein the C ₂ to the original _{ring-Examples 6} monocyclic sikbok summon an amino group, a 2-thienyl group, a 3-thienyl group, 2-frills group, 3-frills group, 2-pyranyl group, 3-pyranyl Amino group, 4-pyranylamino group, 1-pyrrolylamino group, 2-pyrrolylamino group, 3-pyrrolylamino group, 1-imidazolylamino group, 2-imidazolylamino group, 4-imidazolylamino group, 1-pyra Zylamino group, 3-pyrazorylamino group, 4-pyrazorylamino group, 2-thiazolylamino group, 4-thiazolylamino group, 5-thiazolylamino group, 3-isothiazolyl amino group, 4-isothiazolylamino group, 5-iso Thiazolylamino group, 2-oxazolylamino group, 4-oxazolylamino group, 5-oxazolylamino group, 3-isoxazolylamino group, 4-isooxazolylamino group, 5-isooxazolylamino group, 2-isoxazolylamino group, 2-pyridylamino group, 3 -Pyridyl amino group, 4-pyri Amino group, 2-pyridinylamino group, 2-pyrimidinylamino group, 4-pyrimidinylamino group, 5-pyrimidinylamino group, 3-pyridazinylamino group, 4-pyridazinylamino group, 2-1, 3, 4-oxadiazolyl amino group, 2-1, 3, 4-thiadiazolyl amino group, 3-1, 2, 4-oxadiazolyl amino group, 5-1, 2, 4-oxadiazolyl amino group, 3-1, 2, 4- thiadiazolyl amino group, 5-1, 2, 4- thiadiazolyl amino group, 3-1, 2, 5-oxadiazolyl group, 3-1, 2, 5- thiadiazolyl amino group, etc. are mentioned. Can be.

Examples of the C _{5 -9} condensed polycyclic heterocyclic group of 2 to configure the number of atoms of 8-10, 2-benzofuranyl group, 3-benzofuranyl group, 4-benzofuranyl group, 5-benzofuranyl group, 6 -Benzofuranylamino group, 7-benzofuranylamino group, 1-isobenzofuranylamino group, 4-isobenzofuranylamino group, 5-isobenzofuranylamino group, 2-benzothienylamino group, 3-benzothienylamino group , 4-benzothienylamino group, 5-benzothienylamino group, 6-benzothienylamino group, 7-benzothienylamino group, 1-isobenzothienylamino group, 4-isobenzothienylamino group, 5-isobenzothier Nylamino group, 2-clomenylamino group, 3-clomenylamino group, 4-clomenylamino group, 5-clomenylamino group, 6-clomenylamino group, 7-clomenylamino group, 8-clomenylamino group, 1-indoledinylamino group , 2-indoledinylamino group, 3- Indolinylamino group, 5-indoldinylamino group, 6-indoldinylamino group, 7-indoledinylamino group, 8-indoledinylamino group, 1-isoindolylamino group, 2-isoindolylamino group, 4-isoindolylamino group, 5 -Isoindoleylamino group, 1-indolylamino group, 2-indolylamino group, 3-indolylamino group, 4-indolylamino group, 5-indolylamino group, 6-indolylamino group, 7-indolylamino group, 1- Indazolylamino group, 2-indazolylamino group, 3-indazolylamino group, 4-indazolylamino group, 5-indazolylamino group, 6-indazolylamino group, 7-indazolylamino group, 1-furinylamino group, 2-furinyl Amino group, 3-furinylamino group, 6-furinylamino group, 7-furinylamino group, 8-furinylamino group, 2-quinolylamino group, 3-quinolylamino group, 4-quinolylamino group, 5-quinolylamino group, 6-quinolylamino group, 7-quinolylamino group , 8-quinolylamino group, 1-isoquinolylamino group, 3-isoquinolylamino group, 4-isoquinolylamino group, 5-isoquinolylamino group, 6-isoquinolylamino group, 7-isoquinolylamino group, 8 -Isoquinolylamino group, 1-futaradinylamino group, 5-futaradinylamino group, 6-futaradinylamino group, 1-2, 7-naphthyldinylamino group, 3-2, 7-naphthyldinylamino group, 4 -2,7-naphthyldinylamino group, 1-2, 6-naphthyldinylamino group, 3-2, 6-naphthyldinylamino group, 4-2, 6-naphthyldinylamino group, 2-1, 8-naph Tyldinylamino group, 3-1, 8-naphthyldinylamino group, 4-1, 8-naphthyldinylamino group, 2-1, 7-naphthyldinylamino group, 3-1, 7-naphthyldinylamino group, 4- 1,7-naphthyldinylamino group, 5-1, 7-naphthyldinylamino group, 6-1, 7-naphthyldinylamino group, 8-1, 7-naphthyldinylamino group, 2-1, 6-naphthyl Diylamino group, 3 -1, 6-naphthyldinylamino group, 4-1, 6-naphthyldinylamino group, 5-1, 6-naphthyldinylamino group, 7-1, 6-naphthyldinylamino group, 8-1, 6-naph Tyldinylamino group, 2-1, 5-naphthyldinylamino group, 3-1, 5-naphthyldinylamino group, 4-1, 5-naphthyldinylamino group, 6-1, 5-naphthyldinylamino group, 7- 1,5-naphthyldinylamino group, 8-1, 5-naphthyldinylamino group, 2-quinoxalinylamino group, 5-quinoxalinylamino group, 6-quinoxalinylamino group, 2-quinazolinylamino group, 4- Quinazolinylamino group, 5-quinazolinylamino group, 6-quinazolinylamino group, 7-quinazolinylamino group, 8-quinazolinylamino group, 3-cinnolinylamino group, 4-shinnolinylamino group, 5-shin Norinylamino group, 6-cinnolinylamino group, 7-cinnolinylamino group, 8-cinnolinylamino group, 2-puteridinylamino group, 4-puteridinylamino group, 6- puteridi Amino group and the like can be mentioned 7-Puteri pyridinyl group.

The C _{1 - 6} as alkylcarbonyl group, methyl-carbonyl group, ethyl carbonyl group, propyl carbonyl group n-, i- propyl carbonyl group, butyl carbonyl group n-, i- butyl carbonyl group, a s -Butylcarbonylamino group, t-butylcarbonylamino group, 1-pentylcarbonylamino group, 2-pentylcarbonylamino group, 3-pentylcarbonylamino group, i-pentylcarbonylamino group, neopentylcarbonylamino group, t-pentyl Carbonylamino group, 1-hexylcarbonylamino group, 2-hexylcarbonylamino group, 3-hexylcarbonylamino group, etc. are mentioned,

The C _{1 - 6} alkyl sulfone as an amide group, a methanesulfonamide group, a sulfonamide group ethane, n- propane sulfone amide group, a sulfonamide group i- propane, n- butane sulfonamide group, i- butane sulfonamide group, s -Butane sulfone amide group, t-butane sulfone amide group, 1-pentane sulfamide group, 2-pentane sulfonamide group, 3-pentane sulfonamide group, i-pentane sulfonamide group, neopentane sulfonamide group, t-pentane And sulfonamide groups, 1-hexane sulfone amide groups, 2-hexane sulfone amide groups, and 3-hexane sulfone amide groups.

The C _{1 - 6} Examples of alkylaminocarbonyl group, methylamino group, ethylamino group, n- propylamino group, an i- propylamino group, a butylamino group n-, i- butylamino group, a s- butyl amino group, a t- Butylaminocarbonyl group, 1-pentylaminocarbonyl group, 2-pentylaminocarbonyl group, 3-pentylaminocarbonyl group, i-pentylaminocarbonyl group, neopentylaminocarbonyl, t-pentylaminocarbonyl group, 1-hexylaminocarbonyl group, 2- Hexyl amino carbonyl group, 3-hexyl amino carbonyl group, etc. are mentioned,

The di -C _{1 - 6} As the alkylamino group, a dimethylamino group, a diethylamino group, a di -n- propyl aminocarbonyl, di -i- propylamino group, a di -c- propylamino group, a di -n- Butylaminocarbonyl group, di-i-butylaminocarbonyl group, di-s-butylaminocarbonyl group, di-t-butylaminocarbonyl group, di-c-butylaminocarbonyl group, di-1-pentylaminocarbonyl group, di-2-pentylamino Carbonyl group, di-3-pentylaminocarbonyl group, di-i-pentylaminocarbonyl group, dinepentylaminocarbonyl group, di-t-pentylaminocarbonyl group, di-c-pentylaminocarbonyl group, di-1-hexylaminocarbonyl group, di- 2-hexylaminocarbonyl group, di-hexylaminocarbonyl group, di-c-hexylaminocarbonyl group, di (1-methyl-n-pentyl) aminocarbonyl group, di (1, 1, 2-trimethyl-n-propyl) army Carbonyl group, di (1, 2, 2-trimethyl- n-propyl) aminocarbonyl group, branched (3, 3- dimethyl- n-butyl) aminocarbonyl group, methyl (ethyl) aminocarbonyl group, methyl (n-propyl) aminocarbonyl group , Methyl (i-propyl) aminocarbonyl group, methyl (c-propyl) aminocarbonyl group, methyl (n-butyl) aminocarbonyl group, methyl (i-butyl) aminocarbonyl group, methyl (s-butyl) aminocarbonyl group, methyl (t- Butyl) aminocarbonyl group, methyl (c-butyl) aminocarbonyl group, ethyl (n-propyl) aminocarbonyl group, ethyl (i-propyl) aminocarbonyl group, ethyl (c-propyl) aminocarbonyl group, ethyl (n-butyl) aminocarbonyl group, Ethyl (i-butyl) aminocarbonyl group, ethyl (s-butyl) aminocarbonyl group, ethyl (t-butyl) aminocarbonyl group, ethyl (c-butyl) aminocarbonyl group, n-propyl (i-propyl) aminocarbonyl group, n-propyl (c- Lofil) aminocarbonyl group, n-propyl (n-butyl) aminocarbonyl group, n-propyl (i-butyl) aminocarbonyl group, n-propyl (s-butyl) aminocarbonyl group, n-propyl (t-butyl) aminocarbonyl group, n -Propyl (c-butyl) aminocarbonyl group, i-propyl (c-propyl) aminocarbonyl group, i-propyl (n-butyl) aminocarbonyl group, i-propyl (i-butyl) aminocarbonyl group, i-propyl (s-butyl ) Aminocarbonyl group, i-propyl (t-butyl) aminocarbonyl group, i-propyl (c-butyl) aminocarbonyl group, c-propyl (n-butyl) aminocarbonyl group, c-propyl (i-butyl) aminocarbonyl group, c- Propyl (s-butyl) aminocarbonyl group, c-propyl (t-butyl) aminocarbonyl group, c-propyl (c-butyl) aminocarbonyl group, n-butyl (i-butyl) aminocarbonyl group, n-butyl (s-butyl) Aminocarbonyl group, n-butyl (t-butyl) amino Carbonyl group, n-butyl (c-butyl) aminocarbonyl group, i-butyl (s-butyl) aminocarbonyl group, i-butyl (t-butyl) aminocarbonyl group, i-butyl (c-butyl) aminocarbonyl group, s-butyl ( t-butyl) aminocarbonyl group, s-butyl (c-butyl) aminocarbonyl group, t-butyl (c-butyl) aminocarbonyl group, etc. are mentioned,

The C _{1 - 6} as the alkyl group, methyl group, ethyl group, n- propyl group, i- propyl group, a n- butyl group, i- butyl group, a s- butyl group, a t- butyl group, a 1-pentyl group, 2-pentyl carbonyl group, 3-pentyl carbonyl group, i-pentyl carbonyl group, neopentyl carbonyl group, t-pentyl carbonyl group, 1-hexyl carbonyl group, 2-hexyl carbonyl group, 3-hexyl carbonyl group, etc. are mentioned,

The C _{6 - 14} aryl group as phenyl group, biphenyl group o-, m- biphenyl group, p- biphenyl group, a 1-naphthyl group, a 2-naphthyl group, 1-tree do not le group, 2 -Anthryl carbonyl group, 9- anthryl carbonyl group, 1-phenan tricarbonyl group, 2-phenan tricarbonyl group, 3-phenan tricarbonyl group, 4-phenan tricarbonyl group, 9-phenan tricarbonyl group, etc. are mentioned. Can be.

The C _{2 - 9} heteroaryl as a carbonyl group, an oxygen atom, a nitrogen atom, a sulfur atom is 1-3 atom C ₂ to the single or 5-7 won can be combined include the _{ring-6-cyclic} heterocyclic group, and the number of constituent atoms ₉ include a condensed polycyclic heterocyclic group 2 _- 8 ~ C ₅ to 10.

5 to the C ₂ to the 7-membered _ring-6 as the monocyclic sikbok recalled group, a 2-thienyl group, a 3-thienyl group, a 2-furyl group, a 3-furyl group, a 2-pyranyl group, 3-pyranyl Carbonyl group, 4-pyranylcarbonyl group, 1-pyrrolylcarbonyl group, 2-pyrrolylcarbonyl group, 3-pyrrolylcarbonyl group, 1-imidazoryl carbonyl group, 2-imidazoryl carbonyl group, 4-imidazoryl carbonyl group, 1-pyranyl Zyl carbonyl group, 3-pyrazolyl carbonyl group, 4-pyrazolyl carbonyl group, 2-thiazoyl carbonyl group, 4-thiazolyl carbonyl group, 5-thiazoyl carbonyl group, 3-isothiazolyl carbonyl group, 4-isothiazolyl carbonyl group, 5-isoiso Thiazolyl carbonyl group, 2-oxazolyl carbonyl group, 4-oxazolyl carbonyl group, 5-oxazolyl carbonyl group, 3-isooxazoyl carbonyl group, 4-isooxazoryl carbonyl group, 5-isooxazo Carbonyl group, 2-pyridylcarbonyl group, 3-pyridylcarbonyl group, 4-pyridylcarbonyl group, 2-pyridinylcarbonyl group, 2-pyrimidinylcarbonyl group, 4-pyrimidinylcarbonyl group, 5-pyrimidinylcarbonyl group, 3- Pyridazinyl carbonyl group, 4-pyridazinyl carbonyl group, 2-1, 3, 4-oxadiazolyl carbonyl group, 2-1, 3, 4-thiadiazolyl carbonyl group, 3-1, 2, 4-oxadiazolyl carbonyl group , 5-1, 2, 4-oxadiazolyl carbonyl group, 3-1, 2, 4-thiadiazolyl carbonyl group, 5-1, 2, 4-thiadiazolyl carbonyl group, 3-1, 2, 5-oxadia Zyl carbonyl group, 3-1, 2, 5- thiadiazolyl carbonyl group, etc. are mentioned.

Examples of the C _{5 -9} condensed polycyclic heterocyclic group of 2 to configure the number of 8 to 10 atoms, 2-benzofuranyl group, 3-benzofuranyl group, 4-benzofuranyl group, 5-benzofuranyl group, 6 -Benzofuranylcarbonyl group, 7-benzofuranylcarbonyl group, 1-isobenzofuranylcarbonyl group, 4-isobenzofuranylcarbonyl group, 5-isobenzofuranylcarbonyl group, 2-benzothienylcarbonyl group, 3-benzothienylcarbonyl group , 4-benzothienylcarbonyl group, 5-benzothienylcarbonyl group, 6-benzothienylcarbonyl group, 7-benzothienylcarbonyl group, 1-isobenzothienylcarbonyl group, 4-isobenzothienylcarbonyl group, 5-isobenzothiene Nylcarbonyl group, 2-Chlomenylcarbonyl group, 3-Chlomenylcarbonyl group, 4-Chlomenyl carbonyl group, 5-Chlomenyl carbonyl group, 6-Chlomenyl carbonyl group, 7-Chlomenyl carbonyl group, 8-Chlomenyl carbon A carbonyl group, 1-indoledinylcarbonyl group, 2-indoledinylcarbonyl group, 3-indoledinylcarbonyl group, 5-indoldinylcarbonyl group, 6-indoledinylcarbonyl group, 7-indoledinylcarbonyl group, 8-indoledinylcarbonyl group, and 1-isoin Dolylcarbonyl group, 2-isoindolylcarbonyl group, 4-isoindolylcarbonyl group, 5-isoindolylcarbonyl group, 1-indolylcarbonyl group, 2-indolylcarbonyl group, 3-indolylcarbonyl group, 4-indolylcarbonyl group, 5- Indolylcarbonyl group, 6-indolylcarbonyl group, 7-indolylcarbonyl group, 1-indazolylcarbonyl group, 2-indazolylcarbonyl group, 3-indadozolylcarbonyl group, 4-indazolylcarbonyl group, 5-indaindazolyl carbonyl group, 6-indazolyl Carbonyl group, 7-indazolylcarbonyl group, 1-furinylcarbonyl group, 2-furinylcarbonyl group, 3-furinylcarbonyl group, 6-furinylcarbonyl group, 7-furinylcarbonyl group, 8-furinylcarbon Bonyl group, 2-quinolylcarbonyl group, 3-quinolylcarbonyl group, 4-quinolylcarbonyl group, 5-quinolylcarbonyl group, 6-quinolylcarbonyl group, 7-quinolylcarbonyl group, 8-quinolylcarbonyl group, 1-isoquinolyl Carbonyl group, 3-isoquinolylcarbonyl group, 4-isoquinolylcarbonyl group, 5-isoquinolylcarbonyl group, 6-isoquinolylcarbonyl group, 7-isoquinolylcarbonyl group, 8-isoquinolylcarbonyl group, 1-putaradinylcarbonyl group , 5-futaradinylcarbonyl group, 6-futaradinylcarbonyl group, 1-2, 7-naphthyldinylcarbonyl group, 3-2, 7-naphthyldinylcarbonyl group, 4-2, 7-naphthyldinylcarbonyl group, 1- 2, 6-naphthyldinylcarbonyl group, 3-2, 6-naphthyldinylcarbonyl group, 4-2, 6-naphthyldinylcarbonyl group, 2-1, 8-naphthyldinylcarbonyl group, 3-1, 8-naphthyl Dynylcarbonyl group, 4-1, 8-naphthyldinylcarbonyl group, 2-1, 7-naphthyldinylcar Bonyl group, 3-1, 7-naphthyldinylcarbonyl group, 4-1, 7-naphthyldinylcarbonyl group, 5-1, 7-naphthyldinylcarbonyl group, 6-1, 7-naphthyldinylcarbonyl group, 8-1 , 7-naphthyldinylcarbonyl group, 2-1, 6-naphthyldinylcarbonyl group, 3-1, 6-naphthyldinylcarbonyl group, 4-1, 6-naphthyldinylcarbonyl group, 5-1, 6-naphthyldinyl Carbonyl group, 7-1, 6-naphthyldinylcarbonyl group, 8-1, 6-naphthyldinylcarbonyl group, 2-1, 5-naphthyldinylcarbonyl group, 3-1, 5-naphthyldinylcarbonyl group, 4-1, 5-naphthyldinylcarbonyl group, 6-1, 5-naphthyldinylcarbonyl group, 7-1, 5-naphthyldinylcarbonyl group, 8-1, 5-naphthyldinylcarbonyl group, 2-quinoxalinylcarbonyl group, 5-quinox Salinylcarbonyl group, 6-quinoxalinylcarbonyl group, 2-quinazolinylcarbonyl group, 4-quinazolinylcarbonyl group, 5-quinazolinylcarbonyl group, 6-quinazolinylcarbonyl group, 7- Nazolinylcarbonyl group, 8-quinazolinylcarbonyl group, 3-cinnolinylcarbonyl group, 4-cinnolinylcarbonyl group, 5-cinnolinylcarbonyl group, 6-cinnolinylcarbonyl group, 7-cinnolinylcarbonyl group, 8-cin A norinyl carbonyl group, a 2- putridinyl carbonyl group, 4- putridinyl carbonyl group, a 6- putridinyl carbonyl group, a 7- putridinyl carbonyl group, etc. are mentioned.

The C _{1 - 6} alkoxy group, a methoxy group, ethoxy group, n- propoxy group, i- propoxy group, n- butoxycarbonyl group, i- butoxy group, a s- butoxy group, t- portion Oxycarbonyl group, 1-pentyloxycarbonyl group, 2-pentyloxycarbonyl group, 3-pentyloxycarbonyl group, i-pentyloxycarbonyl group, neopentyloxycarbonyl group, t-pentyloxycarbonyl group, 1-hexyloxycarbonyl group, 2-hexyloxycarbonyl group, and 3-hexyloxycarbonyl group, etc. are mentioned,

The C _{1 - 6} As the alkylsulfonyl group, there may be mentioned methane sulfonyl group, trifluoro methane sulfonyl group and ethane sulfonyl group. Examples of the C _{6 -14} aryl sulfonyl group, a benzene sulfonyl group, sulfonyl group, carbonyl bipe o-, m--biphenyl sulfonyl group, p- biphenyl sulfonyl group, 1-naphthalene-sulfonyl, naphthalene-2-sulfonyl group, 1-anthracene Sulfonyl group, 2-anthracenesulfonyl group, 9-anthracenesulfonyl group, 1-phenanthrenesulfonyl group, 2-phenanthrenesulfonyl group, 3-phenanthrenesulfonyl group, 4-phenanthrenesulfonyl group, 9-phenanthrenesulfonyl group, etc. Can be mentioned.

The C _{2 -9} heteroaryl sulfonyl group as, an oxygen atom, a nitrogen atom, a sulfur atom is 1 to 3 atoms of the C ₂ to single or 5-7 won can be combined include the _{ring-6-cyclic} group and PO repeat sohwansul configuration atoms include a group C _{5 -9} condensed polycyclic repeat 2 sohwansul sulfonyl up to 8-10.

5-7 wherein the C ₂ to the member ring _{- 6} as a monocyclic clothing fabric sohwansul group, sulfonyl group, 2-thienyl, 3-thienyl sulfonyl group, 2-furyl sulfonyl group, sulfonyl group 3-furyl, 2-pyranyl Sulfonyl group, 3-pyranylsulfonyl group, 4-pyranylsulfonyl group, 1-pyrrolylsulfonyl group, 2-pyrrolylsulfonyl group, 3-pyrrolylsulfonyl group, 1- imidazorylsulfonyl group, 2-imida Zylsulfonyl group, 4-imidazolyl sulfonyl group, 1-pyrazolyl sulfonyl group, 3-pyrazoryl sulfonyl group, 4-pyrazoryl sulfonyl group, 2-thiazolyl sulfonyl group, 4-thiazolyl sulfonyl group, 5-thia Zylsulfonyl group, 3-isothiazolyl sulfonyl group, 4-isothiazolyl sulfonyl group, 5-isothiazolyl sulfonyl group, 2-oxazolyl sulfonyl group, 4-oxazolyl sulfonyl group, 5-oxazolyl sulfonyl group, 3 -Isoxazolylsulfonyl group, 4-isooxazolylsulfonyl group, 5-isooxazolylsulfonyl group, 2-pyridylsulfonyl group, 3-pyridylsulfonyl group, 4-pyridyl Ponyyl group, 2-pyridinylsulfonyl group, 2-pyrimidinylsulfonyl group, 4-pyrimidinylsulfonyl group, 5-pyrimidinylsulfonyl group, 3-pyridazinyl sulfonyl group, 4-pyridazinyl sulfonyl group , 2-1, 3, 4-oxadiazolyl sulfonyl group, 2-1, 3, 4-thiadiazolyl sulfonyl group, 3-1, 2, 4-oxadiazolyl sulfonyl group, 5-1, 2, 4-oxadiazolyl sulfonyl group, 3-1, 2, 4-thiadiazolyl sulfonyl group, 5-1, 2, 4-thiadiazolyl sulfonyl group, 3-1, 2, 5-oxadiazolyl sulfonyl group, and 3-1, 2, 5- thiadiazolyl sulfonyl group, etc. are mentioned.

Configuration Examples of the C _{5 -9} condensed polycyclic repeat 2 sohwansul Four groups of atoms up to 8-10, 2-benzofuranyl sulfonyl group, sulfonyl group, 3-benzofuranyl, 4-benzofuranyl sulfonyl group, 5-benzofuranyl Nylsulfonyl group, 6-benzofuranylsulfonyl group, 7-benzofuranylsulfonyl group, 1-isobenzofuranylsulfonyl group, 4-isobenzofuranylsulfonyl group, 5-isobenzofuranylsulfonyl group, 2-benzo Thienylsulfonyl group, 3-benzothienylsulfonyl group, 4-benzothienylsulfonyl group, 5-benzothienylsulfonyl group, 6-benzothienylsulfonyl group, 7-benzothienylsulfonyl group, 1-isobenzothier Neylsulfonyl group, 4-isobenzothienylsulfonyl group, 5-isobenzothienylsulfonyl group, 2-chloromenylsulfonyl group, 3-chloromenylsulfonyl group, 4-chloromenylsulfonyl group, 5-chloromenylsulfonyl group, 6-Chlomenylsulfonyl group, 7-Chlomenylsulfonyl group, 8-Chlomenylsulfonyl group, 1-indoledinylsulfonyl group, 2-indoldinylsulfonyl group, 3- Indolinylsulfonyl group, 5-indoledinylsulfonyl group, 6-indoledinylsulfonyl group, 7-indoledinylsulfonyl group, 8-indoledinylsulfonyl group, 1-isoindolylsulfonyl group, 2-isoindolylsulfonyl group, 4 -Isoindolylsulfonyl group, 5-isoindolylsulfonyl group, 1-indolylsulfonyl group, 2-indolylsulfonyl group, 3-indolylsulfonyl group, 4-indolylsulfonyl group, 5-indolylsulfonyl group, 6-indolylsulfonyl group, 7-indolylsulfonyl group, 1-indazolylsulfonyl group, 2-indazolylsulfonyl group, 3-indazolylsulfonyl group, 4-indazolylsulfonyl group, 5-indazolylsulfonyl group, 6 -Indazolyl sulfonyl group, 7-indazolyl sulfonyl group, 1-furinylsulfonyl group, 2-furinylsulfonyl group, 3-furinylsulfonyl group, 6-furinylsulfonyl group, 7-furinylsulfonyl group, 8- Furinylsulfonyl group, 2-quinolylsulfonyl group, 3-quinolylsulfonyl group, 4-quinolylsulfonyl group, 5-quinolylsulfonyl group, 6-quinolylsulfonyl group, 7-quinolylsulfonyl group , 8-quinolylsulfonyl group, 1-isoquinolylsulfonyl group, 3-isoquinolylsulfonyl group, 4-isoquinolylsulfonyl group, 5-isoquinolylsulfonyl group, 6-isoquinolylsulfonyl group, 7- Isoquinolylsulfonyl group, 8-isoquinolylsulfonyl group, 1-putadinylsulfonyl group, 5-putadinylsulfonyl group, 6-putadinylsulfonyl group, 1-2, 7-naphthyldinylsulfonyl group, 3-2, 7-naphthyldinylsulfonyl group, 4-2, 7-naphthyldinylsulfonyl group, 1-2, 6-naphthyldinylsulfonyl group, 3-2, 6-naphthyldinylsulfonyl group, 4- 2, 6-naphthyldinylsulfonyl group, 2-1, 8-naphthyldinylsulfonyl group, 3-1, 8-naphthyldinylsulfonyl group, 4-1, 8-naphthyldinylsulfonyl group, 2-1, 7-naphthyldinylsulfonyl group, 3-1, 7-naphthyldinylsulfonyl group, 4-1, 7-naphthyldinylsulfonyl group, 5-1, 7-naphthyldinylsulfonyl group, 6-1, 7- Naphthyldinylsulfonyl group, 8-1, 7-naphthyldinylsulfonyl group, 2-1, 6-naphthyldinylsulfonyl group, 3 -1, 6-naphthyldinylsulfonyl group, 4-1, 6-naphthyldinylsulfonyl group, 5-1, 6-naphthyldinylsulfonyl group, 7-1, 6-naphthyldinylsulfonyl group, 8-1 , 6-naphthyldinylsulfonyl group, 2-1, 5-naphthyldinylsulfonyl group, 3-1, 5-naphthyldinylsulfonyl group, 4-1, 5-naphthyldinylsulfonyl group, 6-1, 5 -Naphthyldinylsulfonyl group, 7-1, 5-naphthyldinylsulfonyl group, 8-1, 5-naphthyldinylsulfonyl group, 2-quinoxalinylsulfonyl group, 5-quinoxalinylsulfonyl group, 6-quinox Salinylsulfonyl group, 2-quinazolinylsulfonyl group, 4-quinazolinylsulfonyl group, 5-quinazolinylsulfonyl group, 6-quinazolinylsulfonyl group, 7-quinazolinylsulfonyl group, 8-quinazolinyl Sulfonyl group, 3-cinnolinylsulfonyl group, 4-cinnolinylsulfonyl group, 5-cinnolinylsulfonyl group, 6-cinnolinylsulfonyl group, 7-cinnolinylsulfonyl group, 8-cinnolinylsulfonyl group , 2- putridinylsulfonyl group, 4- putridinylsulfonyl group, 6- puteridi And the like sulfonyl group and 7-Puteri pyridinyl sulfonyl group.

Examples of the C _{2 -9} heterocyclic methacrylic group, and the heterocyclic group include monocyclic and bicyclic chukhwan formed from a nitrogen atom, an oxygen atom and a sulfur atom one or more atoms and from 2 to 9 carbon atoms selected from among free, Specifically,

(Tue 26)

Etc. can be mentioned.

In the above formula, a small '-' (meaning a bond) in each ring structure indicates that it can take any position which is substitutable in chemical structure, and does not mean to specify a substitution site.

Expression (a), Expression (b), Expression (c), Expression (d), Expression (f), Expression (g), Expression (h), Expression (j), Expression (k), Expression (m), Expression (n), Expression (o), Expression (p), Expression (q), Expression (r), Expression (s), Expression (t), Expression (u), Expression (i), Expression (w), R ¹⁴ , R ¹⁵ , R ¹⁶ and R in formulas (y), (z), (aa), (ab), (ac), (ad), (ae) and (af) ¹⁷ are each independently,

Hydrogen atom, fluorine atom, chlorine atom, bromine atom, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, n-pentyl group, i-pentyl group, 3, 3-dimethyl-n-butyl Group, methylcarbonyloxymethyl group, ethylcarbonyloxymethyl group, methylcarbonyloxyethyl group, ethylcarbonyloxyethyl group, methylcarbonylaminomethyl group, ethylcarbonylaminomethyl group, methylcarbonylaminoethyl group, ethylcarbonylaminoethyl group, Methoxycarbonylmethyl group, ethoxycarbonylmethyl group, methoxycarbonylethyl group, ethoxycarbonylethyl group, c-propyl group, c-pentyl group, c-hexyl group methoxy group, ethoxy group, n-propoxy group, i-propoxy group, methyl thi group, ethyl thi group, phenyl group, o-biphenylyl group, m-biphenylyl group, p-biphenylyl group, 1-naphthyl group, 2-naphthyl group, 2-pyridyl group, 3 -Pyridyl group, 4-pyridyl group, methylcarbonyloxy group, ethylcarbonyloxy group, n-propyl Carbonyloxy group, i-propylcarbonyloxy group, n-butylcarbonyloxy group, t-butylcarbonyloxy group, methyl amino group, ethyl amino group, n-propyl amino group, i-propyl amino group, n-butyl amino group, dimethyl Amino group, diethyl amino group, di-n-propyl amino group, di-i-propyl amino group, di-n-butyl amino group,

Phenyl amino group, o-biphenylamino group, m-biphenylamino group, p-biphenylamino group, 1-naphthylamino group, 2-naphthylamino group, 2-pyridyl amino group, 3-pyridyl amino group, 4-pyridyl amino group , Methylcarbonylamino group, ethylcarbonylamino group, n-propylcarbonylamino group, i-propylcarbonylamino group, n-butylcarbonylamino group, methane sulfonamide group, ethanesulfonamide group, n-propane sulfonamide group, i -Propane sulfone amide group, n-butane sulfone amide group, methylaminocarbonyl group, ethylaminocarbonyl group, n-propylaminocarbonyl group, i-propylaminocarbonyl group, n-butylaminocarbonyl group, dimethylaminocarbonyl group, diethylaminocarbonyl group, di- n-propylaminocarbonyl group, di-i-propylaminocarbonyl group, di-c-propylaminocarbonyl group, di-n-butylaminocarbonyl group, methylka Carbonyl group, ethylcarbonyl group, n-propylcarbonyl group, i-propylcarbonyl group, n-butylcarbonyl group, phenylcarbonyl group, o-biphenylcarbonyl group, m-biphenylcarbonyl group, p-biphenylcarbonyl group, 1-naphthylcarbonyl group, 2- Naphthylcarbonyl group, 2-pyridylcarbonyl group, 3-pyridylcarbonyl group, 4-pyridylcarbonyl group, methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, i-propoxycarbonyl group, n-butoxycarbonyl group, i- Butoxycarbonyl group, s-butoxycarbonyl group, t-butoxycarbonyl group, methanesulfonyl group, trifluoromethanesulfonyl group, benzenesulfonyl group, o-biphenylsulfonyl group, m-biphenylsulfonyl group, p-biphenylsulfonyl group , 1-naphthalenesulfonyl group, 2-naphthalenesulfonyl group, 2-pyridylsulfonyl group, 3-pyridylsulfonyl group, 4-pyridylsulfonyl group, amino group, cyano group, carbamoyl group, carboxyl group,

(Tue 27)

Is preferred. In the above formula, '-' (meaning a bond) written in each ring structure indicates that it can take any position which is substitutable in chemical structure, and does not mean to specify a substitution site.

Q in said Formula (c), Formula (d), Formula (p), Formula (q), Formula (iii), Formula (w), Formula (ab), Formula (ac), and Formula (ad) is O ( Oxygen atom), S (sulfur atom), SO (sulfinyl group) or SO ₂ (sulfonyl group). In formulas (c), (d), (p), (q), (f), (w), (ab), (ac) and (ad), Q is O (oxygen). Atoms) are preferred.

The partial ring structure A in the formula (11) or formula (12) is

(Tue 28)

Expression (a), Expression (b), Expression (i), Expression (k), Expression (o), Expression (p), Expression (s), Expression (ｖ), Expression (y), Expression (ae), Expression (a), Expression (b), Expression (i), Expression (k), Expression (o), Expression (p), Expression (s) and Expression (ｖ) ), Formula (y), formula (ae), formula (ag) or formula (ah) in R ¹² , R ¹³ , R ¹⁴ , R ¹⁵ and R ¹⁶ will be described.

The partial ring structure of A in Formula (11) or Formula (12),

Expression (a), Expression (b), Expression (i), Expression (k), Expression (o), Expression (p), Expression (s), Expression (ｖ), Expression (y), Expression (ae), Expression (a), Expression (b), Expression (i), Expression (k), Expression (p), Expression (a), Expression (ae) and Expression (ag) ) it will be described with respect to R ¹² and R ¹³ in.

R ¹² and R ¹³ in formula (a), formula (b), formula (i), formula (k), formula (p), formula (i), formula (ae) and formula (ag) are each independently hydrogen atoms, C _{1 -6} alkyl group _- represents a (the alkyl group is a halogen atom, C _{1 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), and optionally may be substituted with amino group or hydroxyl group.).

Each substituent of R ¹² and R ¹³ in formula (a), formula (b), formula (i), formula (k), formula (p), formula (iii), formula (ae) and formula (ag) is specifically Explain.

The C _{1 - 6} alkyl group as a methyl group, trifluoromethyl group, methoxy methyl group, ethyl group, n- propyl, i- propyl, n- butyl, i- butyl, s- butyl, t- butyl, n-pentyl group, 2-pentyl group, 3-pentyl group, i-pentyl group, neopentyl group, 2, 2- dimethyl propyl group, n-hexyl group, 2-hexyl group, 3-hexyl group, 1-methyl -n-pentyl group, a 1, 1, 2-trimethyl-n-propyl group, a 1, 2, 2-trimethyl-n-propyl group, a 3, 3- dimethyl- n-butyl group, etc. are mentioned.

As R ¹² and R ^{13 in} formula (a), formula (b), formula (i), formula (k), formula (p), formula (i), formula (ae) and formula (ag), each independently hydrogen Atom, methyl group, trifluoromethyl group, methoxy methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, n-pentyl group, i-pentyl group, amino group, and hydroxy group are preferable, and more preferably It is a hydrogen atom and a methyl group.

The partial ring structure of A in formula (11) or formula (12) is formula (a), formula (b), formula (i), formula (k), formula (o), formula (p), formula ( s), formula (i), formula (y), formula (ae), formula (ag) or formula (ah) in the case of formula (a), formula (b), formula (k), formula (o), R <^14> , R <^15> and R <^16> in Formula (p), Formula (s), Formula (y), Formula (y), and Formula (ae) are demonstrated. R ¹⁴ , R ^{15 in} formulas (a), (b), (k), (o), (p), (s), (k), (y) and (ae) and R ¹⁶ is each independently a hydrogen atom, a halogen atom or a C1-6 alkyl group (said alkyl group, a halogen atom, a C ₁₆ alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), amino group, a hydroxy group, C _{1 - 6} alkylamino group, a di -C _{1 - 6} alkylaminocarbonyl group, C _{1 - 6} alkylcarbonyloxy group, C _{1 -6} alkylcarbonyl group (the alkylcarbonyloxy group and the alkylcarbonyl group may be optionally substituted with a halogen atom May be)

C _{1 - 6} alkylcarbonyl group, C _{3 - 6} shows a may be optionally substituted with an alkoxycarbonyl group) _{- 8} cycloalkyl group or C _1..

R ¹⁴ , R ^{15 in} formulas (a), (b), (k), (o), (p), (s), (k), (y) and (ae) And each atom and each substituent of R ¹⁶ will be described in detail.

As said halogen atom, a fluorine atom, a chlorine atom, a bromine atom, and an oxo atom are mentioned,

The C _{1 - 6} alkyl group as a methyl, trifluoro methyl, ethyl, n- propyl, i- propyl, n- butyl, i- butyl, s- butyl, t- butyl, n- pentyl , 2-pentyl group, 3-pentyl group, i-pentyl group, neopentyl group, 2, 2-dimethyl propyl group, n-hexyl group, 2-hexyl group, 3-hexyl group, 1-methyl-n-pen Tyl group, 1, 1, 2-trimethyl-n-propyl group, 1, 2, 2-trimethyl-n-propyl group, and 3, 3- dimethyl-n-butyl group, methylcarbonyloxymethyl group, ethylcarbonyl Oxymethyl group, methylcarbonyloxyethyl group, ethylcarbonyloxyethyl group, methylcarbonylaminomethyl group, ethylcarbonylaminomethyl group, methylcarbonylaminoethyl group, ethylcarbonylaminoethyl group, methoxycarbonylmethyl group, ethoxycarbonylmethyl group , Methoxycarbonylethyl group, trifluoromethoxycarbonylmethyl group, ethoxycarbonylethyl group, and the like. The C _{1 - 6} As the alkylcarbonyl group, methyl-carbonyl group, a trifluoromethyl-carbonyl group, ethyl carbonyl group, propyl carbonyl group n-, i- propyl carbonyl group, an n- butyl carbonyl group, i -Butylcarbonylamino group, s-butylcarbonylamino group, t-butylcarbonylamino group, 1-heptylcarbonylamino group, 2-heptylcarbonylamino group, 3-pentylcarbonylamino group, i-pentylcarbonylamino group, neopentyl Carbonylamino group, t-pentylcarbonylamino group, 1-hexylcarbonylamino group, 2-hexylcarbonylamino group, 3-hexylcarbonylamino group, etc. are mentioned,

The C _{3 -} Examples ₈ cycloalkyl group, a c- propyl group, a c- butyl group, 1-methyl -c- propyl group, a 2-methyl -c- propyl group, a c- pentyl group, 1-methyl -c- butyl Carbonyl group, 2-methyl-c-butylcarbonyl group, 3-methyl-c-butylcarbonyl group, 1,2-dimethyl-c-propylcarbonyl group, 2,3-dimethyl-c-propylcarbonyl group, 1-ethyl-c-propyl Carbonyl, 2-ethyl-c-propylcarbonyl, c-hexylcarbonyl, c-heptylcarbonyl, c-octylcarbonyl, 1-methyl-c-hexylcarbonyl, 2-methyl-c-hexylcarbonyl, 3-methyl- c-hexylcarbonyl group, 1, 2-dimethyl-c-hexylcarbonyl group, 2,3-dimethyl-c-propylcarbonyl group, 1-ethyl-c-propylcarbonyl group, 1-methyl-c-pentylcarbonyl group, 2-methyl -c-pentylcarbonyl group, 3-methyl-c-pentylcarbonyl group, 1-ethyl-c-butylcarbonyl group ㅣ, 2-ethyl-c-butylcarbonyl group, 3-ethyl-c-butylcarbonyl group, 1,2-dimethyl- c-butyl Carbonyl group, 1,3-dimethyl-3-c-butylcarbonyl group, 2,2-dimethyl-c-butylcarbonyl group, 2,3-dimethyl-c-butylcarbonyl group, 2,4-dimethyl-c-butylcarbonyl group, 3 , 3-dimethyl-c-butylcarbonyl group, 1-n-propyl-c-propylcarbonyl group, 2-n-propyl-c-propylcarbonyl group, 1-i-propyl-c-propylcarbonyl group, 2-i-propyl -c-propylcarbonyl group, 1, 2, 2, -trimethyl-c-propylcarbonyl group, 1, 2, 3-trimethyl-c-propylcarbonyl group, 2, 2, 3-trimethyl-c-propylcarbonyl group, 1-ethyl- 2-methyl-c-propylcarbonyl group, 2-ethyl-1-methyl-c-propylcarbonyl group, 2-ethyl-2-methyl-c-propylcarbonyl group, 2-ethyl-3-methyl-c-propylcarbonyl group, etc. are mentioned. Can and

The C _{1 - 6} alkoxycarbonyl group as the methoxy group, ethoxy group, n- propoxy group, i- propoxy group, n- butoxycarbonyl group, i- butoxy group, a s- butoxy group, t- butoxy Carbonyl group, 1-pentyloxycarbonyl group, 2-pentyloxycarbonyl group, 3-pentyloxycarbonyl group, i-pentyloxycarbonyl group, neopentyloxycarbonyl group, t-pentyloxycarbonyl group, 1-hexyloxycarbonyl group, 2-hexyloxycarbonyl group and 3 -Hexyloxycarbonyl group, etc. are mentioned.

R ¹⁴ , R ^{15 in} formulas (a), (b), (k), (o), (p), (s), (k), (y) and (ae) And R ¹⁶ is

Each independently hydrogen atom, fluorine atom, chlorine atom, bromine atom, methyl group, trifluoromethyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, n-pentyl group, i-pentyl group, methyl Carbonyloxymethyl group, ethylcarbonyloxymethyl group, methylcarbonyloxyethyl group, ethylcarbonyloxyethyl group, methylcarbonylaminomethyl group, ethylcarbonylaminoethyl group, methylcarbonylaminoethyl group, ethylcarbonylaminoethyl group, methoxycarbon Carbonyl methyl group, ethoxycarbonylmethyl group, methoxycarbonylethyl group, trifluoromethoxycarbonylmethyl group, ethoxycarbonylethyl group are preferable, or a hydrogen atom, a fluorine atom, a chlorine atom, a methyl group, a trifluoromethyl group, an ethyl group, n-propyl group, i-propyl group, methylcarbonyloxymethyl group, ethylcarbonyloxymethyl group, methylcarbonylaminoethyl group, ethylcarbonylaminoethyl group, methoxy Cycarbonylmethyl group and trifluoromethoxycarbonylmethyl group are more preferable.

The partial ring structure of A in said Formula (11) or Formula (12) is said Formula (p) and Formula (i), and Q in said Formula (p) or Formula (i) is O (oxygen atom), S (Sulfur atom), SO (sulfinyl group) or SO ₂ (sulfonyl group). Q in formula (p) or (iv) is preferably O (oxygen atom).

R <^9> , R <^10> , W, X, Y, and Z in said Formula (13) are demonstrated.

Expression (13) in the R ⁹ and R ¹⁰ each independently represent a hydrogen atom, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 - 6} alkoxy group

(The alkoxy group may be optionally substituted with a halogen atom.)

Or optionally substituted by a hydroxy group.),

C _{6 - 14} aryl group

(Wherein the aryl group, a halogen atom, a hydroxy group, a nitro group, a cyano group, C _{1 - 6} alkyl

(Said alkyl group, a halogen atom, C _{1 - 6} alkoxy group

(The alkoxy group may be optionally substituted with a halogen atom.)

Or optionally substituted by a hydroxy group.),

C _{1 - 6} alkoxy group

(The alkoxy group may be optionally substituted with a halogen atom.)

May be optionally substituted with).

R ⁹ in formula (13) And each substituent of R ¹⁰ will be described in detail.

The C _{1 - 6} alkyl group as a methyl group, trifluoromethyl group, methoxy methyl group, ethyl group, n- propyl, i- propyl, n- butyl, i- butyl, s- butyl, t- butyl, 1-pentyl group, 2-pentyl group, 3-pentyl group, i-pentyl group, neopentyl group, 2, 2-dimethyl propyl group, 1-hexyl group, 2-hexyl group, 3-hexyl group, 1-methyl -n-pentyl group, 1, 1, 2-trimethyl-n-propyl group, 1, 2, 2-trimethyl-n-propyl group, 3, 3- dimethyl-n-butyl group, etc. are mentioned,

The C _{6 - 14} As the aryl group,

Phenyl group, o-biphenylyl group, m-biphenylyl group, p-biphenylyl group, 1-naphthyl group, 2-naphthyl group, 1- anthryl group, 2-anthryl group, 9- anthryl group, 1 -Phenanthryl group, 2-phenanthryl group, 3-phenanthryl group, 4-phenanthryl group, 9-phenanthryl group, etc. are mentioned.

R <^9> and R <^10> in Formula (13) has preferable a methyl group, a trifluoromethyl group, and an ethyl group, More preferably, it is a methyl group.

Expression (13) in W is a hydrogen atom, a hydroxy group, C _{1 - 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), halogen atom, C _{1 - 4} alkyl or C _{1 - 6} alkyl sulfonamide Group (The alkyl group and alkyl sulfone amide group may be optionally substituted with a halogen atom.).

Each atom and each substituent of W in Formula (13) are demonstrated concretely.

The C _{1 - 6} alkoxy group includes a methoxy group, an ethoxy group, n- propoxy, i- propoxy, n- butoxy, i- butoxy, s- butoxy group, t- butoxy group, 1-pentyl Oxy, 2-pentyl oxy, 3-pentyl oxy, i-pentyl oxy, neopentyl oxy, 2, 2-dimethyl propoxy, 1-hexyl oxy, 2-hexyl oxy, 3-hexyl Oxy group, 1-methyl-n-pentyl oxy group, 1, 1, 2-trimethyl-n-propoxy group, 1, 2, 2-trimethyl-n-propoxy group, and 3, 3-dimethyl-n -Butoxy group, etc. are mentioned,

As said halogen atom, a fluorine atom, a chlorine atom, a bromine atom, and an oxo atom are mentioned,

Examples ₄ alkyl group, _wherein the C ₁

Methyl group, trifluoro methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group, etc. are mentioned,

The C _{1 - 6} alkyl sulfone as an amide group, a methanesulfonamide group, a trifluoro methane sulfone amide group, a sulfonamide group ethane, n- propane sulfone amide group, a sulfonamide group i- propane, n- butane sulfonamide group, an i -Butane sulfone amide group, s-butane sulfone amide group, t-butane sulfone amide group, 1-pentane sulfonamide group, 2-pentane sulfonamide group, 3-pentane sulfonamide group, i-pentane sulfonamide group, neopentane And sulfonamide groups, t-pentane sulfonamide groups, 1-hexane sulfone amide groups, 2-hexane sulfone amide groups, and 3-hexane sulfone amide groups.

W in Formula (13) is a hydrogen atom, a hydroxyl group, a fluorine atom, a chlorine atom, a bromine atom, a methyl group, a trifluoromethyl group, an ethyl group, a methoxy group, an ethoxy group, n-propoxy group, i-propoxy group, methane sulfone Amide group, trifluoromethane sulfone amide group, ethane sulfone amide group, n-propane sulfone amide group, i-propane sulfone amide group, n-butane sulfone amide group are preferable,

More preferably, they are a hydrogen atom, a hydroxyl group, a fluorine atom, a methyl group, a trifluoromethyl group, an ethyl group, a methoxy group, a methane sulfone amide group, and a trifluoro methane sulfone amide group.

X in the formula 13, represents an NR ^20, N is a nitrogen atom,

R ²⁰ is a hydrogen atom or a C _{1 - 4} alkyl group is a.

Each substitution base of R <^20> in X of Formula (13) is demonstrated concretely.

The C _{1 - 4} As the alkyl group, there may be mentioned methyl, ethyl, n- propyl, i- propyl, n- butyl, i- butyl, s- butyl group and t- butyl group.

R ²⁰ in X in the formula (13) is preferably a hydrogen atom, a methyl group, or an ethyl group.

Y in Formula (13) is a bond, SO (sulfinyl group) or SO ₂ (sulfonyl group), and a bond and SO ₂ are preferable.

Z in the formula (13), C _{1 - 4} alkyl

(Wherein the C _{1 - 4} alkyl groups, 1-5 halogen atoms or a phenyl group

(Wherein the phenyl group, C _{1 -} may also optionally be substituted by ₄ alkyl group.)

May be optionally substituted.)

Or phenyl group

(Wherein the phenyl group, C _{1 -. 4} may be optionally substituted with an alkyl group), represents a.

Each substituent of Z in Formula (13) is demonstrated concretely.

The C _{1 - 4} As the alkyl group, there may be mentioned a methyl group, trifluoromethyl group, ethyl group, n- propyl, i- propyl, n- butyl, i- butyl, s- butyl group and t- butyl group .

Z in Formula (13) is preferably a methyl group, a trifluoromethyl group, an ethyl group, an n-propyl group, an i-propyl group, or a phenyl group.

Optical activity represented by any one of said Formula (1), Formula (1 '), Formula (2), Formula (2'), Formula (3), Formula (3 '), Formula (4), and Formula (4'). The titanium complex is used as a catalyst, and the amount of the optically active titanium complex is 0.001 to 100 mol%, based on the chromium compound represented by formula (10), formula (11), formula (12) or formula (13). It is a range, the range of 0.01-20 mol% is preferable, and the range of 0.3-5 mol% is more preferable.

Optical activity is represented by any one of said formula (1), formula (1 '), formula (2), formula (2'), formula (3), formula (3 '), formula (4) and formula (4'). The solvent which uses a titanium complex as a catalyst and uses for a subsidiary epoxidation reaction is a halogen type solvent, an aromatic hydrocarbon solvent, an ester solvent, an ether solvent, or a nitrile solvent as a non-flotone organic solvent, As the organic solvent of the above, it is an alcohol solvent. Examples of the halogen solvent include dichloromethane, chloroform, 1,2-dichloroethane and chlorobenzene. Examples of the aromatic hydrocarbon solvent include benzene and toluene. Examples of the ester solvent include ethyl acetate and the like. Examples of the ether solvent include tetrahydrofuran, diethyl ether and the like, and examples of the nitrile solvent include butyronitrile, propionitrile and acetonitrile. Examples of the alcohol solvents include methanol, ethanol, i-propanol, and the like, as well as mixtures of the above solvents. When the aqueous solution of hydrogen peroxide (hydrogen peroxide solution) is used in the present reaction, the organic phase and the aqueous phase may be separated by mixing with an organic solvent that does not dissolve in water. However, such a two-phase solvent may also be used as the reaction solvent of the present invention. There is a number. Preferred solvents are dichloromethane, 1,2-dichloroethane, chlorobenzene, toluene, ethyl acetate, or a mixture of these solvents, which are non-flotone organic solvents.

As a manufacturing operation, when a chromate compound, an optically active titanium complex, and an oxidizing agent are added to an organic solvent, reaction will advance. As an addition order, it is preferable to add an oxidizing agent to the solution which consists of an organic solvent, a chromium compound, and an optically active titanium complex.

Specific examples of the oxidizing agent used in the reaction include iodine benzene, sodium hypochlorite, m-chloroperbenzoic acid, Okison (DuPont®), hydrogen peroxide, urea-hydrogen peroxide adduct (UHP), oxadiridine, N -Methyl morpholine oxide (NMO), t-butyl hydrofel oxide (TBHP), cumene hydropearl oxide (CHP), and a mixture of these oxidizing agents are mentioned. Among them, hydrogen peroxide water, urea-hydrogen peroxide adduct (UHP) and mixtures of these oxidants are preferred. The concentration in the case where the oxidizing agent is hydrogen peroxide water may be in the range of 1 to 100% (% by weight), but is preferably in the range of 5 to 60% (% by weight).

As the usage-amount of the oxidizing agent used for reaction, although the range of 1-10 equivalent is mentioned with respect to the chromium compound represented by Formula (10), Formula (11), Formula (12), or Formula (13), 1-3 equivalents The range of is preferable.

As addition method of an oxidizing agent, division addition and continuous addition are mentioned besides batch addition.

In the case of continuous addition, the addition rate is preferably in a range in which the internal temperature does not increase rapidly in the reaction solvent system, specifically, in the range of 0.01 to 40000 equivalents per hour, more preferably in the range of 0.05 to 0.3 equivalents per hour. . In addition, divided addition is a method of dividing and adding the oxidizing agent to p times (p is arbitrary integer). Dividing may be equal part or boiling part, and p has the preferable range of 2-100.

Although range of -78 degreeC-solvent reflux temperature or solvent melting point temperature-solvent reflux temperature to use is mentioned, reaction range is -20-50 degreeC, and the range of 0-35 degreeC is more preferable. .

Although the pressure in a reaction system can mention the range of 10 kPa-1100 kPa, 15 kPa-200 kPa are preferable. By pressurizing, it can react at temperature higher than the solvent reflux temperature at the time of normal pressure.

As long as the reaction is carried out, an optically active titanium complex serving as a catalyst can be further added to shorten the reaction time. Moreover, the reaction time can be shortened by adding an oxidizing agent further.

After completion | finish of reaction, distillation operation, silica gel column chromatography, separation | separation extraction operation, recrystallization operation, or the above operation can be carried out by separate-separation purification, and the target optically active chromium oxide compound can be obtained.

The optical purity of the obtained optically active chromium oxide compound can be analyzed by optically active high performance liquid chromatography analysis, optically active gas chromatography analysis, or optical photometry.

Hereinafter, although an Example demonstrates in detail, this invention is not limited to these.

In addition, in the optically active chromium oxide compound in an Example, the absolute arrangement of subsidiary carbon does not turn out to exist. About these compounds, an asterisk (*) is attached | subjected to the absolute arrangement notation in the subsidiary carbon and a compound name in the figure, and shows that description of a figure and a compound name is a reverse absolute arrangement notation.

Synthesis of Optically Active Titanium Sararen Complexes (A), (B) and (C)

The optically active titanium sararen complexes (A), (B) and (C) used in the examples are described in Non Patent Document 8 (Angew. Chem. Int. Ed. (2005), 44, 4935-4939). It was prepared according to the method.

(Tue 29)

The optically active titanium sallan complex (D) represented by the following formula is

(Tue 30)

 Salan Liege (42 ')

1.1 mol of titanium tetraisopropoxide [Ti (Oi-Pr) ₄ ] is 25-28 with respect to 1 mol of sallan ligands 42 'in the dichloromethane reaction solvent of a sallan ligand 42'. It stirred at 5 degreeC and stirred for 5 hours, and after continuing to add water at 25-28 degreeC, the reaction solution was stirred for 12 hours. Thereafter, the reaction solvent was removed to obtain a composition organism, which was then recrystallized from dichloromethane to obtain an optically active titanium complex (D).

Pale yellow white solid

MS (CSI) = 1082, 2163

The optically active titanium salane complexes (E) and (F) were also obtained by the same production method as described above.

(Tue 31)

 (Example 1)

Synthesis of (3S, 4S) -6-acetamide 3,4-epoxy-3,4-dihydro 2,2-dimethyl-7-nitro-2H-1-benzopyran (Compound (I))

(Tue 32)

6-acetamide 2, 2-dimethyl-7-nitro at 28 ° C. in a dichloromethane solution (3 ml) of an optically active titanium sararen complex (B) (38 mg, 0.021 mmol) (1.0 mol% based on substrate). -2H-1-benzopyran (0.54 g, 2.1 mmol) was added. While the reaction solution was stirred, 7.5% hydrogen peroxide water (1.4 g, 3.1 mmol) was added at 28 ° C. over 10 hours. The addition start time of 7.5% hydrogen peroxide water was added after 14 hours as the reaction start time at 7.5% hydrogen peroxide water (0.1 g, 0.2 mmol) at 28 ° C. Furthermore, stirring was continued at 28 degreeC for 19 hours. After completion of the reaction, dichloromethane (6 ml) and distilled water (6 ml) were added to the reaction solution to separate the organic phase, and the crude product was combined with the organic phase extracted from dichloromethane (6 ml) from the aqueous phase, and concentrated to give a column. Purification by chromatography gave Compound (I) (0.49 g, yield 86%, optical purity of 99.9% ee or more) as a yellow powder.

Analysis conditions: Column name: CHIRALPAK® OJ-RH, eluent acetonitrile / methanol / 0.01M sodium chloride aqueous solution = 1 / 3/5 (mm / mm / mm), flow rate 1.5 ml / min, column temperature: 40 ° C, holding time Product of reaction: 15.9 minutes (3S, 4S), enantiomer: 11.7 minutes (3R, 4R), measured wavelength: 242 nm.

¹ H-NMR (CDCl ₃ ) δ; 1.27 (s, 3H), 1.59 (s, 3H), 2.28 (s, 3H), 3.55 (d, J = 4.1 Hz, 1H), 3.97 (d, J = 4.1 Hz, 1H), 7.64 (s, 1H), 8.79 (s, 1H), 10.10 (br, 1H)

(Example 2)

Synthesis of (3R, 4R) -6-acetamide 3,4-epoxy-3,4-dihydro 2,2-dimethyl-7-nitro-2H-1-benzopyran (Compound (II))

(Tue 33)

6-acetamide 2, 2-dimethyl-7-nitro at 30 ° C. in a dichloromethane solution (3 ml) of an optically active titanium salan complex (E) (25.6 mg, 0.021 mmol) (1.0 mol% relative to substrate). -2H-1-benzopyran (537.4 mg, 2.1 mmol) was added. While stirring the reaction solution, 30% hydrogen peroxide water (302.7 mg, 2.7 mmol) was added at 30 ° C. over 1 second. Thereafter, stirring was continued for 7 hours at 30 ° C. After the completion of the reaction, dichloromethane and distilled water were added to the reaction solution to separate an organic phase, and the crude product concentrated by further combining the organic phase extracted from dichloromethane from an aqueous phase was purified by column chromatography to obtain Compound (II) (0.53 g). , Yield 93%, optical purity 99.9% ee or more) was obtained as a yellow powder.

Analysis conditions: Column name CHICHILPAK OJ-RH, eluent acetonitrile / methanol / 0. 01 M aqueous sodium chloride solution = 1/3/5 (Pa / V / Pa), flow rate 1. 5 mL / min, column temperature # 40 ° C., holding time The product of this reaction: 13. 4 minutes (3R, 4R), Current isomer: 17. 5 min (3 S, 4 S), measurement wavelength: 242 nm.

1 H-NMR (CDCl 3) δ; 27 (s, 3 H), 1. 59 (s, 3 H), 2. 28 (s, 3 H), 3. 55 (d, J = 4.2 Hz, 1 H), 3. 97 (d, J = 4.5 Hz, 1 H), 7.63 (s, 1 H), 8. 79 (s, 1 H), 10. 09 (br, 1 H)

(Example 3)

Synthesis of (3S, 4S) -3,4-epoxy-3,4-dihydro 2,2-dimethyl-6-nitro-2H-1-benzopyran (Compound (III))

Tue 34

To a dichloromethane solution (8 ml) of an optically active titanium sararen complex (B) (73 mg, 0.041 mmol) (2.0 mol% relative to a substrate) at 25 ° C., 2,2-dimethyl-6-nitro-2H-1- Benzopyran (0.41 g, 2.0 mmol) was added. While stirring the reaction solution, 30% hydrogen peroxide solution (0.24 g, 2.1 mmol) was added at 25 ° C. over 2 seconds. The start time of addition of 30% hydrogen peroxide water was stirred at 25 ° C. for 27 hours as the reaction start time. After the completion of the reaction, dichloromethane (6 ml) and distilled water (6 ml) were added to the reaction solution to separate the organic phase, and the crude product concentrated by combining the organic phase extracted from dichloromethane (6 ml) from the aqueous phase was concentrated. Purification by chromatography gave compound (III) (0.43 g, yield 97%, optical purity of 99.9% ee or more) as a white yellow powder.

Analysis conditions: Column name CHIRALCEL® OD-H, eluent n-hexane / i-propanol = 9/1 (dl / v), flow rate 1.0 ml / min, column temperature 占 40 占 폚, holding time The product of this reaction: 9.6 minutes ( 3S, 4S), isomer: 8.4 minutes (3R, 4R), measurement wavelength: 300 nm.

¹ H-NMR (CDCl ₃ ) δ; 1.33 (s, 3H), 1.63 (s, 3H), 3.57 (d, J = 4Hz, 1H), 4.00 (d, J = 4Hz, 1H), 6.89 (d, J = 9.1 Hz, 1H), 8.15 (dd, J = 9.1, 2.8 Hz, 1H), 8. 31 (d, J = 2.8 Hz, 1H)

(Example 4)

Synthesis of (3S, 4S) -3,4-epoxy-3,4-dihydro 2,2-dimethyl-6-nitro-2H-1-benzopyran (Compound (III))

Expression (43 ')

(Tue 35)

Titanium tetraisopropoxide [Ti (Oi-Pr) ₄ ] (2) in a dichloromethane solution (0.3 ml) of a sallan ligand (4.9 mg, 0.0080 mmol) (4.0 mol% based on substrate) represented by 3 mg, 0.0080 mmol) was added. After 1 hour of stirring at 20 ° C, 2,2-dimethyl-6-nitro-2H-1-benzopyran (41 mg, 0.20 mmol) was added. 30% hydrogen peroxide water (0.034 g, 0.3 mmol) was divided into 3 parts, the reaction solution was stirred, the first time was added at 20 ° C, the second time after 30 minutes, and the third time after 1 hour. The reaction liquid was sampled after stirring for 24 hours at 20 degreeC as reaction start time of the time of addition of the 1st 30% hydrogen peroxide solution, and the reaction conversion ratio was analyzed by HPLC. The conversion rate to compound (III) was 99% or more, and optical purity was 99% ee.

Analytical conditions: Column name CHIRALPAK® AD-RH3 extension, eluent acetonitrile / 20 mM (pH8) phosphate buffer = 6/4 (mm / ml), flow rate: 1.0 ml / min, column temperature: 40 ° C, storage and holding time : 15.8 minutes (3S, 4S), isomer: 12.6 minutes (3R, 4R), measurement wavelength: 330 nm.

(Example 5)

Synthesis of (3R, 4R) -3,4-epoxy-3,4-dihydro 2,2-dimethyl-6-nitro-2H-1-benzopyran (Compound (IV))

(Tue 36)

To a dichloromethane solution (6 ml) of an optically active titanium salane complex (E) (48 mg, 0.040 mmol) (2.0 mol% based on substrate) at 20 ° C., 2,2-dimethyl-6-nitro-2H-1-benzo Piran (0.41 g, 2.0 mmol) was added. 30% hydrogen peroxide water (0.24 g, 2.1 mmol) was divided into 3 parts, the 1st was added at 20 degreeC, stirring the reaction solution, the 2nd was added after 30 minutes, and the 3rd after 1 hour. After the first addition time of 30% hydrogen peroxide water was stirred at 20 ° C. for 24 hours as the reaction start time, dichloromethane (5 mL) and distilled water (5 mL) were added to the reaction solution to separate the organic phase, and the aqueous phase was again water-phase. The crude product, which was combined with the organic phase extracted twice from dichloromethane (5 ml, 3 ml), was concentrated and purified by column chromatography to obtain compound (IV) (0.41 g, yield 94%, optical purity of 99.9% ee or more). Was obtained as a white yellow powder. Analysis conditions: Column name CHIRALPAK AD-RH3 extension, eluent acrylonitrile / 20 mM (pH8) phosphate buffer = 6/4 (ｖ / ｖ), flow rate 1.0 mL / min, column temperature 40 ° C, storage holding time Product of the reaction : 12.6 minutes (3R, 4R), isomer: 15.8 minutes (3S, 4S), measurement wavelength: 330 nm.

1 H-NMR (CDCl 3) δ; 33 (s, 3H), 1.62 (s, 3H), 3.58 (d, J = 4Hz, 1H), 4.00 (d, J = 4Hz, 1H ), 6. 89 (d, J = 8.6 Hz, 1 H), 8. 14 (dd, J = 8.6, 3. 0 Hz, 1 H), 8. 30 (d, J = 3. 0 Hz, 1 H)

(Example 6)

Synthesis of (3R, 4R) -3,4-epoxy-3,4-dihydro 2,2-dimethyl-6-nitro-2H-1-benzopyran (Compound (IV))

To a dichloromethane solution (8 ml) of an optically active titanium sararen complex (A) (73 mg, 0.041 mmol) (2.0 mol% relative to a substrate) at 25 ° C., 2,2-dimethyl-6-nitro-2H-1- Benzopyran (0.41 g, 2.0 mmol) was added. While stirring the reaction solution, 30% hydrogen peroxide water (0.24 g, 2.1 mmol) was added at 25 ° C. over 2 seconds. After that, stirring was continued at 25 ° C., and the reaction solution was sampled after 8 hours as the start time of the addition of 30% hydrogen peroxide water, and the reaction conversion rate was analyzed by HPLC. The conversion to compound (IV) was 99% or more, and the optical purity was 96% ee.

Analysis conditions: Column name: CHIRALPAK® AD-RH, Eluent Acetonitrile / 20 mM (pH8) Phosphoric Acid Buffer = 6/4 (mm / min), Flow Rate: 1.0 ml / min, Column Temperature: 40 ° C, Storage and Maintenance Time 5.2 minutes (3R, 4R), Current isomer: 6. 1 minute (3S, 4S), measurement wavelength: 330 nm.

(Example 7)

(3S *, 4S *)-3, 4-epoxy-3, 4-dihydro 2, 2-dimethyl-7-nitro-6-methoxy-2H-1-benzopyran (compound (V), * is, Relative placement)

(Tue 37)

To a dichloromethane solution (8 ml) of an optically active titanium sararen complex (B) (71 mg, 0.040 mmol) (2.0 mol% relative to a substrate) at 25 ° C., 2,2-dimethyl-7-nitro-6-methoxy -2H-1-benzopyran (0.47 g, 2.0 mmol) was added. While stirring the reaction solution, 30% hydrogen peroxide water (0.24 g, 2.1 mmol) was added at 25 ° C. over 2 seconds. Stirring was continued at 25 ° C. for 19 hours as the start time of addition of 30% hydrogen peroxide water. After the completion of the reaction, dichloromethane (3 ml) and distilled water (3 ml) were added to the reaction liquid to separate the organic phase, and the crude product was combined by concentrating the organic phase extracted from dichloromethane (3 ml) from the aqueous phase and concentrated. Purification by chromatography gave Compound (V) (0.50 g, yield 99%, optical purity of 99.9% ee or more) as a yellow oil phase.

Analysis conditions: Extension of column name CHIRALPAK AD-RH, eluent acetonitrile / 20 mM (pH8) phosphate buffer = 6/4 (ｖ / ｖ), flow rate: 0.8 ml / min, column temperature: 40 ° C, storage holding time Of product: 12.1 minutes, reisomer: 11.3 minutes, measurement wavelength: 225 nm.

¹ H-NMR (CDCl ₃ ) δ; 1.26 (s, 3H), 1.59 (s, 3H), 3.53 (d, J = 4Hz, 1H), 3. 90 (d, J = 4Hz, 1H ), 3.95 (s, 3H), 7.08 (s, 1H), 7.33 (s, 1H)

(Example 8)

(3S *, 4S *)-3, 4-epoxy-3, 4-dihydro 2, 2-dimethyl-7-nitro-6-methoxy-2H-1-benzopyran (compound (V), * is, Relative placement)

Expression (41 ＇)

(Tue 38)

Titanium tetraisopropoxide [Ti (Oi-Pr) ₄ ] (5.7 mg) in a dichloromethane solution (0.9 ml) of a sallan ligand (14 mg, 0.020 mmol) (4.0 mol% relative to a substrate) represented by , 0.020 mmol) was added. After stirring at 20 ° C for 1 hour, 2,2-dimethyl-7-nitro-6-methoxy-2H-1-benzopyran (0.118 g, 0.50 mmol) was added. 30% hydrogen peroxide water (0.085 g, 0.75 mmol) was divided into 3 parts, the first time was added at 20 DEG C while stirring the reaction solution, the second time after 30 minutes, and the third time after 1 hour. After the first addition of 30% hydrogen peroxide water was stirred for 24 hours at 20 ° C as the reaction start time, the reaction solution was sampled and the reaction conversion rate was analyzed by HPLC. The conversion to compound (V) was 99% or more, and the optical purity was 99% ee.

Analysis conditions: Extension of column name CHIRALPAK AD-RH, eluent acetonitrile / 20 mM (pH8) phosphate buffer solution = 6/4 (ｖ / ｖ), flow rate: 0.5 ml / min, column temperature: 40 ° C, storage holding time Of product: 18.3 minutes, isomer: 17.5 minutes, measurement wavelength: 225 nm.

(Example 9)

(3R *, 4R *)-3, 4-epoxy-3, 4-dihydro 2, 2-dimethyl-7-nitro-6-methoxy-2H-1-benzopyran (compound (V '), * , Relative placement).

To a dichloromethane solution (7 ml) of an optically active titanium salan complex (E) (48 mg, 0.040 mmol) (2.0 mol% based on substrate) at 25 ° C., 2,2-dimethyl-7-nitro-6-methoxy- 2H-1-benzopyran (0.47 g, 2.0 mmol) was added. 30% hydrogen peroxide water (0.24 g, 2.1 mmol) was divided into 3 parts, the 1st was added at 20 degreeC, stirring the reaction solution, the 2nd was added after 30 minutes, and the 3rd after 1 hour. The reaction time of the first 30% hydrogen peroxide solution was stirred at 20 ° C. for 24 hours as the reaction start time, and then dichloromethane (5 mL) and distilled water (5 mL) were added to the reaction solution, and the organic phase was separated. The crude product concentrated by combining the organic phase extracted twice from dichloromethane (5 mL, 3 mL) was purified by column chromatography to obtain Compound (VIII) (0.48 g, yield 96%, optical purity more than 99.9% ee). Was obtained in the form of a yellow oil.

Analysis conditions: Extension of column name CHIRALPAK AD-RH, eluent acetonitrile / 20 mM (pH8) phosphate buffer solution = 6/4 (ｖ / ｖ), flow rate: 0.5 ml / min, column temperature: 40 ° C, storage holding time Of product: 17.5 minutes, reisomer: 18.3 minutes, measurement wavelength: 225 nm.

¹ H-NMR (CDCl ₃ ) δ; 1.26 (s, 3H), 1.58 (s, 3H), 3.54 (d, J = 4.5 Hz, 1H), 3. 91 (d, J = 4.5 Hz, 1H ), 3.95 (s, 3H), 7.09 (s, 1H), 7.32 (s, 1H)

(Example 10)

(3R *, 4R *)-3, 4-epoxy-3, 4-dihydro 2, 2-dimethyl-7-nitro-6-methoxy-2H-1-benzopyran (compound (V '), * , Relative placement).

To a dichloromethane solution (8 ml) of an optically active titanium sararen complex (A) (71 mg, 0.040 mmol) (2.0 mol% relative to a substrate) at 25 ° C., 2,2-dimethyl-7-nitro-6-methoxy -2H-1-benzopyran (0.47 g, 2.0 mmol) was added. While stirring the reaction solution, 30% hydrogen peroxide water (0.24 g, 2.1 mmol) was added at 25 ° C. over 2 seconds. The reaction liquid was sampled after 18 hours as the start time of addition of 30% hydrogen peroxide water, and the reaction conversion ratio was analyzed by HPLC. The conversion to compound (V ′) was 99% or more, and the optical purity was 99% ee.

Analysis conditions: Extension of column name CHIRALPAK AD-RH, eluent acetonitrile / 20 mM (pH8) phosphate buffer = 6/4 (ｖ / ｖ), flow rate: 0.8 ml / min, column temperature: 40 ° C, storage holding time Of product: 11.3 minutes, reisomer: 12.1 minutes, measurement wavelength: 225 nm.

(Example 11)

(3S *, 4S *)-3, 4-epoxy-3, 4-dihydro 2, 2-dimethyl-7-nitro-2H- 1- benzopyran (Compound (VI), * shows a relative arrangement. ) Synthesis

(Tue 39)

To a dichloromethane solution (4 ml) of an optically active titanium sararen complex (B) (36 mg, 0.020 mmol) (2.0 mol% relative to a substrate) at 25 ° C., 2,2-dimethyl-7-nitro-2H-1- Benzopyran (0.21 g, 1.0 mmol) was added. While stirring the reaction solution, 30% hydrogen peroxide water (0.12 g, 1.1 mmol) was added over 2 seconds. The start time of addition of 30% hydrogen peroxide water was stirred at 25 ° C. for 27 hours as the reaction start time. After the completion of the reaction, dichloromethane (2 ml) and distilled water (2 ml) were added to the reaction solution to separate the organic phase, and the crude product was combined with the organic phase extracted from dichloromethane (2 ml) from the aqueous phase, and concentrated to give a column. Purification by chromatography gave compound (VI) (0.43 g, yield 99%, optical purity 99.4% ee) as a yellow powder.

Analysis conditions: Column name: CHIRALPAK® AD-RH, Eluent Acetonitrile / 20 mM (pH8) Phosphate buffer = 6/4 (ｖ / ｖ), Flow rate: 1.0 ml / min, Column temperature: 40 ° C, Storage and holding time Product of the reaction: 9. 2 minutes, ordinary isomer: 4. 9 minutes, measurement wavelength: 220 nm.

¹ H-NMR (CDCl ₃ ) δ; 1.29 (s, 3H), 1.62 (s, 3H), 3.58 (d, J = 4.4 Hz, 1H), 3. 97 (d, J = 4.4 Hz, 1H) , 7.50 (d, J = 8.3 Hz, 1 H), 7.67 (dd, J = 8.3, 2.2 Hz, 1H), 7. 80 (d, J = 2.2 Hz, 1H)

(Example 12)

(3S *, 4S *)-3, 4-epoxy-3, 4-dihydro 2, 2-dimethyl-7-nitro-2H-1-benzopyran (Compound (VI), * shows a relative arrangement. ) Synthesis

To a dichloromethane solution (6 ml) of an optically active titanium salan complex (F) (48 mg, 0.040 mmol) (2.0 mol% based on substrate) at 25 ° C., 2,2-dimethyl-7-nitro-2H-1-benzo Piran (0.41 g, 2.0 mmol) was added. 30% hydrogen peroxide water (0.25 g, 2.2 mmol) was divided into 3 parts, the 1st was added at 20 degreeC, stirring the reaction solution, the 2nd was added after 30 minutes, and the 3rd after 1 hour. The addition time of the 1st 30% hydrogen peroxide water was stirred at 20 degreeC for 24 hours as reaction start time. After the completion of the reaction, dichloromethane (5 ml) and distilled water (5 ml) were added to the reaction solution to separate the organic phase, and the organic phase extracted twice from dichloromethane (5 ml, 3 ml) from the aqueous phase was combined and concentrated. Iii) The product was purified by column chromatography to give compound (VI) (0.44 g, yield 98%, optical purity 99.9% ee) as yellow crystals.

Analysis conditions: Extension of column name CHIRALPAK AD-RH, eluent acetonitrile / 20 mM (pH8) phosphate buffer = 6/4 (ｖ / ｖ), flow rate 1.0 mL / min, column temperature 40 ° C, storage holding time Of product: 25.2 minutes, ordinary isomer: 13.9 minutes, measurement wavelength: 220 nm.

¹ H-NMR (CDCl ₃ ) δ; 1.29 (s, 3H), 1.61 (s, 3H), 3.60 (d, J = 4.5 Hz, 1H), 3. 99 (d, J = 4.5 Hz, 1H) , 7.52 (d, J = 8.3 Hz, 1H), 7.62 (d, J = 2.1 Hz, 1H), 7.70 (dd, J = 8.3, 2.1 Hz, 1H)

(Example 13)

(3R *, 4R *)-3, 4-epoxy-3, 4-dihydro 2, 2-dimethyl-7-nitro-2H-1-benzopyran (compound (VI '), * represents a relative arrangement) Synthesis of.)

To a dichloromethane solution (4 ml) of an optically active titanium sararen complex (A) (36 mg, 0.020 mmol) (2.0 mol% based on a substrate) at 25 ° C., 2,2-dimethyl-7-nitro-2H-1- Benzopyran (0.21 g, 1.0 mmol) was added. While stirring the reaction solution, 30% hydrogen peroxide water (0.12 g, 1.1 mmol) was added at 25 ° C. over 2 seconds. After that, stirring was continued at 25 ° C, and the reaction solution was sampled after 24 hours as the start time of the addition of 30% hydrogen peroxide water, and the reaction conversion rate was analyzed by HPLC. The conversion rate to compound (VI ') was 99% or more, and optical purity was 99% ee.

Analysis conditions: Column name: CHIRALPAK® AD-RH, Eluent Acetonitrile / 20 mM (pH8) Phosphate buffer = 6/4 (ｖ / ｖ), Flow rate: 1.0 ml / min, Column temperature: 40 ° C, Storage and holding time Product of the reaction: 4.9 minutes, Current isomer: 9.2 minutes, Measurement wavelength 220 nm.

(Example 14)

(3R *, 4R *)-3, 4-epoxy-3, 4-dihydro 2, 2-dimethyl-7-nitro-2H-1-benzopyran (compound (VI '), * represents a relative arrangement) Synthesis of.)

To a dichloromethane solution (3 ml) of an optically active titanium salan complex (E) (24 mg, 0.020 mmol) (2.0 mol% based on substrate) at 20 ° C., 2,2-dimethyl-7-nitro-2H-1-benzo Piran (0.205 g, 1.0 mmol) was added. 30% hydrogen peroxide water (0.12 g, 1.1 mmol) was divided into 3 parts, the reaction solution was stirred, the 1st time was added at 20 degreeC, the 2nd time after 30 minutes, and the 3rd time after 1 hour. The reaction solution was sampled after stirring for 24 hours at 20 degreeC as reaction start time of the 1st addition time of 30% hydrogen peroxide water, and the reaction conversion ratio was analyzed by HPLC. The conversion rate to compound (VI ') was 99% or more, and optical purity was 99% ee.

Analysis conditions: Extension of column name CHIRALPAK AD-RH, eluent acetonitrile / 20 mM (pH8) phosphate buffer = 6/4 (ｖ / ｖ), flow rate 1.0 mL / min, column temperature 40 ° C, storage holding time Of product: 13.9 minutes, isomer: 25.2 minutes, measurement wavelength: 220 nm.

(Example 15)

(3S *, 4S *)-3, 4-epoxy-6- fluorine-3, 4-dihydro 2, 2-dimethyl-8-nitro-2H- 1- benzopyran (compound (VII), * is relative Synthesis)

(Tue 40)

To a dichloromethane solution (4 ml) of an optically active titanium sararen complex (B) (37 mg, 0.021 mmol) (2.0 mol% relative to a substrate), 6-fluoro-2, 2-dimethyl-8-nitro- at 25 ° C. 2H-1-benzopyran (0.23 g, 1.0 mmol) was added. While stirring the reaction solution, 30% hydrogen peroxide water (0.12 g, 1.1 mmol) was added at 25 ° C. over 2 seconds. The start time of addition of 30% hydrogen peroxide water was stirred at 25 ° C. for 29 hours as the reaction start time. After the completion of the reaction, dichloromethane (2 ml) and distilled water (2 ml) were added to the reaction solution to separate the organic phase, and the crude product concentrated by combining the organic phases extracted from dichloromethane (2 ml) from the aqueous phase was concentrated. Purification by chromatography gave compound (VII) (0.23 g, yield 94%, optical purity more than 99.9% ee) as a yellow powder.

Analysis conditions: Column name: CHIRALPAK® AD-RH for three consecutive lengths, eluent acetonitrile / 20 mM (pH8) phosphate buffer = 6/4 (ｖ / ｖ), flow rate: 0.5 ml / min, column temperature: 40 ° C, storage holding time Reaction product: 17.4 minutes, Current isomer: 18.1 minutes, Measurement wavelength: 220 nm.

¹ H-NMR (CDCl ₃ ) δ; 1.33 (s, 3H), 1.64 (s, 3H), 3.57 (d, J = 4Hz, 1H), 3. 94 (d, J = 4Hz, 1H ), 7.35 (dd, J = 4,7.1 Hz, 1H), 7.56 (dd, J = 4.4, 7.9 Hz, 1H)

(Example 16)

Of (3S *, 4S *)-3, 4-epoxy-6- fluorine-2, 2-dimethyl-8-nitro-2H- benzopyran (compound (VII), * shows a relative arrangement.) synthesis

Formula (44 ＇)

(Tue 41)

Titanium tetraisopropoxide [Ti (Oi-Pr) ₄ ] (11 mg, 0.040 mmol) at 25 ° C. in a dichloromethane solution (1.7 mL) (43 mg, 0.080 mmol) (4.0 mol% based on substrate). ) Was added. After stirring at 20 ° C for 1 hour, 6-fluor-3, 4-dihydro 2,2-dimethyl-8-nitro-2H-1-benzopyran (0.446 g, 2.0 mmol) was added. 30% hydrogen peroxide water (0.25 g, 2.2 mmol) was divided into 3 parts, the 1st was added at 20 degreeC, stirring the reaction solution, the 2nd was added after 30 minutes, and the 3rd after 1 hour. The addition time of the 1st 30% hydrogen peroxide water was stirred at 20 degreeC for 40 hours as reaction start time. After the completion of the reaction, dichloromethane (5 ml) and distilled water (5 ml) were added to the reaction solution to separate the organic phase, and the organic phase extracted twice from dichloromethane (5 ml, 3 ml) from the aqueous phase was combined and concentrated. Iii) The product was purified by column chromatography to give compound (VII) (0.43 g, yield 90%, optical purity of 99.9% ee or more) in the form of a yellow oil.

Analysis conditions: Column name CHICHILPAK AD-RH three times in succession, eluent acetonitrile / 20 mM (pH8) phosphate buffer = 6/4 (ｖ / ｖ), flow rate ㎖ 0.5 ml / min, column temperature 40 ℃, storage holding time Product of this reaction: 16.8 minutes, Current isomer: 17.3 minutes, Measurement wavelength: 220 nm.

¹ H-NMR (CDCl ₃ ) δ; 1.33 (s, 3H), 1.63 (s, 3H), 3.60 (d, J = 4.5Hz, 1H), 3.98 (d, J = 4.5Hz, 1H ), 7.38 (dd, J = 3.0, 7.4 Hz, 1H), 7.54 (dd, J = 3.0, 7.4 Hz, 1H)

(Example 17)

(3R *, 4R *)-3, 4-epoxy-6-fluor-3, 4-dihydro 2, 2-dimethyl-8-nitro-2H-1-benzopyran (compound (VII '), * is, Relative placement)

To a dichloromethane solution (4 ml) of an optically active titanium sararen complex (A) (37 mg, 0.021 mmol) (2.0 mol% based on substrate), 6-fluoro-2, 2-dimethyl-8-nitro- at 25 ° C. 2H-1-benzopyran (0.23 g, 1.0 mmol) was added. While stirring the reaction solution, 30% hydrogen peroxide water (0.12 g, 1.1 mmol) was added at 25 ° C. over 2 seconds. The reaction liquid was sampled 3 hours after the start time of addition of 30% hydrogen peroxide solution, and the reaction conversion ratio was analyzed by HPLC. The conversion to compound (VII ′) was 76%, and the optical purity was 99% ee.

Analysis condition: Column name CHICHILPAK AD-RH three times in succession, eluent acetonitrile / 20 mM (pH8) phosphate buffer = 6/4 (ｖ / ｖ), flow rate 0.5 ml / min, column temperature 40 ° C, storage holding time Reaction product: 18.1 minutes, Current isomer: 17.4 minutes, Measurement wavelength: 220 nm.

(Example 18)

(3R *, 4R *)-3, 4-epoxy-6-fluor-3, 4-dihydro 2, 2-dimethyl-8-nitro-2H-1-benzopyran (compound (VII '), * is, Relative placement)

To a dichloromethane solution (3 ml) of an optically active titanium salane complex (E) (24 mg, 0.020 mmol) (2.0 mol% based on substrate), 6-fluoro-2, 2-dimethyl-8-nitro-2H at 20 ° C. -1-benzopyran (0.23 g, 1.0 mmol) was added. 30% hydrogen peroxide water (0.12 g, 1.1 mmol) was divided into 3 parts, the 1st was added at 20 degreeC, stirring the reaction solution, the 2nd was added after 30 minutes, and the 3rd after 1 hour. The reaction solution was sampled after stirring for 24 hours at 20 degreeC as reaction start time of the 1st addition time of 30% hydrogen peroxide water, and the reaction conversion ratio was analyzed by HPLC. The conversion rate to compound (VII ') was 96%, and optical purity was 99% ee or more.

Analysis condition: Column name CHICHILPAK AD-RH three times in succession, eluent acetonitrile / 20 mM (pH8) phosphate buffer = 6/4 (ｖ / ｖ), flow rate 0.5 ml / min, column temperature 40 ° C, storage holding time Reaction product: 17.3 minutes, Current isomer: 16.8 minutes, Measurement wavelength: 220 nm.

(Example 19)

(3R *, 4R *)-(3, 4- epoxy-2, 2, 9-trimethyl-3, 4-dihydro 2H-pyrano [2,3-g] quinolin-7-yl) -methyl acetate (Compound (VIII ') and * represent relative arrangement.) Synthesis

(Tue 42)

To a dichloromethane solution (3 ml) of optically active titanium sararen complex (A) (71 mg, 0.040 mmol) (1.9 mol% relative to substrate) at 28 ° C., (2, 2, 9-trimethyl-2H-pyrano [2,3-g] quinolin-7-yl) -methyl acetate (0.61 g, 2.1 mmol) was added. While stirring the reaction solution, 7.5% hydrogen peroxide water (1.4 g, 3.1 mmol) was added at 28 ° C. over 10 hours. The addition start time of 7.5% hydrogen peroxide water was added after 5 hours as reaction start time 7.5% hydrogen peroxide water (0.1 g, 0.2 mmol) was further added at 28 degreeC. After that, stirring was continued at 28 ° C. for 14 hours. After the completion of the reaction, dichloromethane (6 ml) and distilled water (6 ml) were added to the reaction solution to separate the organic phase, and the crude product was combined by concentrating the organic phase extracted from dichloromethane (6 ml) from the aqueous phase and concentrated. Purification by chromatography gave the compound (VIII ') (0.65 g, 99% yield, 99.9% optical purity or more) as a yellow oil.

Analysis conditions: Column name: CHIRALPAK® AD-RH, eluent acetonitrile / 20 mM (pH8) phosphate buffer solution = 6/4 (ｖ / ｖ), flow rate 1.0 ml / min, column temperature: 40 ° C, storage holding time Product of this reaction: 3.9 min, Current isomer: 9.3 min, Measurement wavelength 254 nm.

¹ H-NMR (CDCl ₃ ) δ; 1.30 (s, 3H), 1.65 (s, 3H), 2.19 (s, 3H), 2.62 (d, J = 0.8 Hz, 3H), 3.61 (d, J = 4.4 Hz, 1H), 4.15 (d, J = 4.4 Hz, 1H), 5.30 (s, 2H), 7. 26 (s, 1H), 7.32 (s, 1H), 8.10 (s, 1H)

(Example 20)

(3R *, 4R *)-(3, 4- epoxy-2, 2, 9-trimethyl-3, 4-dihydro 2H-pyrano [2,3-g] quinolin-7-yl) -methyl acetate Synthesis of (Compound (VIII '))

To a dichloromethane solution (1.2 ml) of an optically active titanium salan complex (D) (6.2 mg, 0.006 mmol) (5.0 mol% relative to a substrate) at 28 ° C., (2, 2, 9-trimethyl-2H-pyrano [2,3-g] quinolin-7-yl) -methyl acetate (34.2 mg, 0.12 mmol) was added and 30% hydrogen peroxide solution (8.5 mg, 0.075 mmol) was stirred for 28 seconds while stirring the reaction solution. Add at 캜. 20 minutes after the start time of addition of 30% hydrogen peroxide water was added as the reaction start time, further 30% hydrogen peroxide water (8.5 mg, 0.075 mmol) was added at 28 DEG C over 1 second. After that, stirring was continued at 28 ° C, and after 3 hours, the reaction solution was sampled and the reaction conversion rate was analyzed by HPLC. The conversion to compound (VIII ′) was 80%, and the optical purity was 99% ee.

Analysis conditions: Column name: CHIRALPAK® AD-RH, Eluent Acetonitrile / 20 mM (pH8) Phosphate buffer solution = 6/4 (ｖ / ｖ), Flow rate: 1.0 mL / min, Column temperature: 40 ° C, Storage holding time Product of this reaction: 10.2 Minutes, regioisomer: 4.1 minutes, measured wavelength: 254 nm.

(Example 21)

(3R *, 4R *)-(3, 4- epoxy-2, 2, 9-trimethyl-3, 4-dihydro 2H-pyrano [2, 3-g] kinolin-7-yl) -methyl Synthesis of Acetate (Compound (VIII '), * represents relative arrangement.)

To a dichloromethane solution (4 ml) of an optically active titanium salan complex (E) (48 mg, 0.040 mmol) (2.0 mol% based on substrate) at 20 ° C., (2, 2, 9-trimethyl-2H-pyrano [ 2,3-g] quinolin-7-yl) -methyl acetate (0.595 g, 2.0 mmol) was added. 30% hydrogen peroxide water (0.34 g, 3.0 mmol) was divided into 3 parts, the 1st was added at 20 degreeC, stirring the reaction solution, the 2nd was added after 30 minutes, and the 3rd after 1 hour. Stirring was continued for 24 hours at 20 degreeC after that as addition time of reaction time of the 1st 30% hydrogen peroxide solution as reaction start time. After the completion of the reaction, dichloromethane (5 ml) and distilled water (5 ml) were added to the reaction solution to separate the organic phase, and the organic phase extracted twice from dichloromethane (5 ml, 3 ml) from the aqueous phase was combined and concentrated. Viii) The product was purified by column chromatography to give the compound (VIII ') (0.61 g, yield 97%, optical purity 99.3% ee) as a yellow powder.

Analysis conditions: Extension of column name CHIRALPAK AD-RH, eluent acetonitrile / 20 mM (pH8) phosphate buffer = 6/4 (ｖ / ｖ), flow rate 1.0 mL / min, column temperature 40 ° C, storage holding time Of product: 11.2 minutes, isomer: 26.6 minutes, measurement wavelength: 320 nm.

¹ H-NMR (CDCl ₃ ) δ; 1.30 (s, 3H), 1.65 (s, 3H), 2.19 (s, d, J = 1.9 Hz, 3H), 2.60 (s, 3H), 3.60 (dd, J = 4.5Hz, 1.9Hz, 1H), 4.14 (d, J = 4.5Hz, 1H), 5.30 (s, 2H), 7.25 (s, 1H), 7.31 (s, 1H), 8.10 (s, 1H )

(Example 22)

(3S *, 4S *)-7-chloro-3, 4-epoxy-2, 2, 9-trimethyl-3, 4-dihydro 2H-pyrano [2, 3-g] chinoline (Compound (IX ), * Indicates relative placement.)

(Tue 43)

To a dichloromethane solution (2 ml) of an optically active titanium sararen complex (F) (120 mg, 0.10 mmol) (10 mol% relative to a substrate), 7-chloro-2, 2, 9-trimethyl-2H at 20 ° C. -Pyrano [2,3-g] quinoline (0.26 g, 1.0 mmol) was added. 30% hydrogen peroxide water (0.17 g, 1.5 mmol) was divided into 3 parts, the 1st was added at 20 degreeC, stirring the reaction solution, the 2nd was added after 30 minutes, and the 3rd after 1 hour. Stirring was continued at 20 degreeC for 26 hours as the reaction start time of the addition time of the 1st 30% hydrogen peroxide water. After the completion of the reaction, dichloromethane (5 ml) and distilled water (5 ml) were added to the reaction solution to separate the organic phase, and the organic phase extracted twice from dichloromethane (5 ml, 3 ml) from the aqueous phase was combined and concentrated. Iii) The product was purified by column chromatography to obtain compound (IX) (0.21 g, yield 77%, optical purity of 99.9% ee or more) as a pale yellow powder.

Analysis conditions: Extension of column name CHIRALPAK AD-RH, eluent acetonitrile / 20 mM (pH8) phosphate buffer = 6/4 (ｖ / ｖ), flow rate 1.0 mL / min, column temperature 40 ° C, storage holding time Of product: 42.1 minutes, isomer: 21.7 minutes, measurement wavelength: 220 nm.

¹ H-NMR (CDCl ₃ ) δ; 1.30 (s, 3H), 1.64 (s, 3H), 2.56 (s, 3H), 3.61 (d, J = 4.2 Hz, 1H), 4.13 (d, J = 4.2 Hz, 1 H), 7.15 (s, 1H), 7.27 (s, 1H), 8.00 (s, 1H)

(Example 23)

(3R *, 4R *)-7-chloro-3, 4-epoxy-2, 2, 9-trimethyl-3, 4-dihydro 2H-pyrano [2,3-g] quinoline (Compound (IX ' ), * Indicates relative placement.)

Salean Liberation Ceremony (44)

Tue 44

Titanium tetraisopropoxide [Ti (Oi-Pr) ₄ ] (2.8 mg, 0.010 mmol) was added to (27 mg, 0.050 mmol) (10 mol% based on substrate) in dichloromethane solution (0.5 mL) at 20 ° C. Added. After 1 hour of stirring at 20 ° C, 7-chloro-2, 2, 9-trimethyl-2H-pyrano [2,3-g] quinoline (0.130 g, 0.50 mmol) and dichloromethane (1 mL) were added. It was. 30% hydrogen peroxide water (0.085 g, 0.75 mmol) was divided into 3 parts, the reaction solution was stirred, the first time was added at 20 ° C, the second time 30 minutes, and the third time after 1 hour. The reaction liquid was sampled after stirring for 45 hours at 20 degreeC as reaction start time of the addition time of the 1st 30% hydrogen peroxide water, and the reaction conversion ratio was analyzed by HPLC. The conversion to compound (IX ') was 99% or more, and the optical purity was 99% ee.

Analysis conditions: Extension of column name CHIRALPAK AD-RH, eluent acetonitrile / 20 mM (pH8) phosphate buffer = 6/4 (ｖ / ｖ), flow rate 1.0 mL / min, column temperature 40 ° C, storage and holding time Of product: 21.7 minutes, isomer: 42.1 minutes, measurement wavelength: 220 nm.

(Example 24)

(3S *, 4S *)-3, 4-epoxy-3, 4-dihydro 2, 2-dimethyl-7- dimethanesulfonylamino 6-methoxy-2H-1-benzopyran (Compound (X), * Indicates relative placement.)

(Tue 45)

To a dichloromethane solution (1 ml) of an optically active titanium salan complex (F) (12 mg, 0.010 mmol) (2.0 mol% based on substrate) at 20 ° C., 2,2-dimethyl-7-dimethanesulfonylamino 6- Methoxy-2H-1-benzopyran (0.18 g, 0.50 mmol) was added. 30% hydrogen peroxide water (0.085 g, 0.775 mmol) was divided into 3 parts, the reaction solution was stirred, the first time was added at 20 ° C, the second time 30 minutes, and the third time after 1 hour. After stirring the first addition time of 30% hydrogen peroxide water at 20 ° C. for 30 hours as the reaction start time, dichloromethane (2 mL) and distilled water (2 mL) were added to the reaction solution to separate the organic phase, and the aqueous phase was again water-phase. The crude product, which was combined with the organic phase extracted twice from dichloromethane (2 mL, 1 mL), was purified by column chromatography, and the compound (X) (0.18 g, yield 97.5%, optical purity 99%) was white. Obtained as a powder.

Analysis conditions: Extension of column name CHIRALPAK AD-RH, eluent acetonitrile / 20 mM (pH8) phosphate buffer solution = 3/7 (ｖ / ｖ), flow rate 1.0 ml / min, column temperature 40 ° C, storage and holding time Of product: 19.8 minutes, isomer: 18.6 minutes, measurement wavelength: 320 nm.

¹ H-NMR (CDCl ₃ ) δ; 1.26 (s, 3H), 1.55 (s, 3H), 3.35 (s, 3H), 3.42 (s, 3H), 3.49 (d, J = 4.5 Hz, 1H) , 3.88 (s, 3H), 3.88 (d, J = 4.5Hz, 1H), 6.77 (s, 1H), 7.00 (s, 1H)

(Example 25)

(3R *, 4R *)-3, 4-epoxy-3, 4-dihydro 2, 2-dimethyl-7- dimethanesulfonylamino 6-methoxy-2H-1-benzopyran (Compound (X ') , * Indicates relative placement.)

To a dichloromethane solution (1 ml) of an optically active titanium salan complex (E) (12 mg, 0.010 mmol) (2.0 mol% relative to a substrate) at 20 ° C., 2,2-dimethyl-7-dimethanesulfonylamino 6- Methoxy-2H-1-benzopyran (72 mg, 0.20 mmol) was added. 30% hydrogen peroxide water (0.034 g, 0.3 mmol) was divided into 3 parts, the reaction solution was stirred, the first time was added at 20 ° C, the second time after 30 minutes, and the third time after 1 hour. After the first addition time of 30% hydrogen peroxide water was stirred for 48 hours at 20 ° C as the reaction start time, the reaction solution was sampled and the reaction conversion rate was analyzed by HPLC. The conversion to compound (X ′) was 99%, and the optical purity was 99% ee.

Analysis conditions: Extension of column name CHIRALPAK AD-RH, eluent acetonitrile / 20 mM (pH8) phosphate buffer solution = 3/7 (ｖ / ｖ), flow rate 1.0 ml / min, column temperature 40 ° C, storage and holding time Of product: 18.5 minutes, isomer: 20.0 minutes, measurement wavelength: 320 nm.

(Example 26)

(3S *, 4S *)-3, 4-epoxy-3, 4-dihydro 2, 2-dimethyl-7- zimethane thru niramino 6-methoxy-2H-1-benzopyran (Compound (X) , * Indicates relative placement.)

To a dichloromethane solution (0.5 ml) of an optically active titanium sararen complex (C) (16 mg, 0.010 mmol) (2.0 mol% relative to a substrate) at 20 ° C., 2,2-dimethyl-7-dimethanesulfonylamino 6 -Methoxy-2H-1-benzopyran (72 mg, 0.20 mmol) was added. 30% hydrogen peroxide water (0.034 g, 0.30 mmol) was divided into 3 parts, the reaction solution was stirred, the first time was added at 20 ° C, the second time after 30 minutes, and the third time after 1 hour. After stirring the first addition time of 30% hydrogen peroxide water for 24 hours at 20 degreeC as reaction start time, the reaction liquid was sampled and the reaction conversion ratio was analyzed by HPLC. The conversion to compound (X) was 83%, and the optical purity was 99% ee.

Analysis conditions: 3 columns of column name CHIRALPAK AD-RH, eluent acetonitrile / 20 mM (pH8) phosphate buffer solution = 3/7 (ｖ / ｖ), flow rate 1.0 mL / min, column temperature, 40 ° C, storage holding time Of product: 19.8 minutes, isomer: 18.6 minutes, measurement wavelength: 320 nm.

According to the present invention, an optically active chromium oxide compound having a high optical purity of 99% ee or more can be obtained in a high yield of 90% or more without using a separation operation for optically dividing a target product, and benzopyrans effective for the treatment of arrhythmia. It can be used sufficiently as an important intermediate of a compound. Therefore, this invention is industrially useful.

Claims (25)

Expression (1), Expression (1 '), Expression (2), Expression (2'), Expression (3), Expression (3 '), Expression (4) and Expression (4'). (Tue 1)

R ¹ in (Equation (1), formula (1 ') and Expression (2), Formula (2'), Formula (3), Formula (3 '), Formula (4) and (4') is a hydrogen atom, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy groups, C _{6 - 12} aryloxy or C _{6 -22} aryl group (the aryl group, C _{1 -4} alkyl group (said alkyl group, halogen atom optionally may be substituted), C _{1 -.. 7} is an alkoxy group, or a benzyloxy group which optionally may be substituted, optically active or optically inactive denotes a), R ² is a hydrogen atom, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy groups, C _{6 - 18} aryl group, and, _{- 12} aryloxy or C ₆ R ³ is C _{1 - 4} alkyl group, C _{6 - 18} aryl group, or the two R ³ is with the case of forming the ring, represents a divalent group _of C _{3 -5,} R ⁴ are each independently a hydrogen atom, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a denotes a nitro group or a cyano group, M is in the TiJ ¹ J ² (TiJ ¹ J ^2, Ti denotes a titanium atom, J ¹ and J ² are, each independently, a halogen atom, C _{1 - 4} show an alkoxide, or the J ¹ and J ² Together to represent an oxygen atom, or J ¹ and J ² are taken together to form a ring; (Tue 2)

(In formula, O represents an oxygen atom, O is represented by following formula (6) as O-E-O in Formula (1), and it is O-E-O in Formula (1 '). In formula (2), it is represented by the following formula (7) as O-E-O, and in formula (2 '), it is represented by the following formula (7') as O-E-O, In (3), it is represented by following formula (8) as O-E-O, It is represented by following formula (8 ') as O-E-O in formula (3'), and as O-E-O in formula (4). It is represented by following formula (9), In (4 '), it is represented by following formula (9') as O-E-O, (Tue 3)

b is an integer of ^1-10 , and R <^1> , R <^2> , R <^3> and R <^4> are the same as the above. ), Formula (11), formula (12), or formula (13) (Tue 4)

(Formula (10) in R ^5, R ^6, R ⁷ and R ⁸ are, each independently, a hydrogen atom, a cyano group, a nitro group, a halogen atom, a C _{1 -4} alkyl group (said alkyl group, a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, C _1-4 alkoxycarbonyl group (the alkoxy group, an alkylcarbonyloxy group, an alkyl carbonyl . a carbonyl group and alkoxycarbonyl group may be arbitrarily substituted with halogen atom) it may also optionally be substituted with a), C _{1 -4} alkoxy group (the alkoxy group, a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 - 4} alkoxy group, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, C _1-4 alkoxycarbonyl group (the alkoxy group, an alkylcarbonyloxy group, an alkyl-carbonyl group and alkoxycarbonyl group, halogen May be optionally substituted with an atom). Optionally may be substituted), C _{1 -. 4} alkylcarbonyl group (the alkylcarbonyl group is a halogen atom, C _{6 -10} aryl group (the C _{6 - 10} aryl group is a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 - 4} alkyl, or C _{1 -. 4} may be an optionally substituted alkoxy group), may also optionally be substituted with a), C _{1 -. 4} alkyl-carbonyl (N-C _{1 - 4} alkyl) amino group (wherein the alkylcarbonyl (N- alkyl) amino group may be arbitrarily substituted with halogen atom), C _{1 -4} alkoxycarbonyl group (the alkoxy group, there may be arbitrarily substituted with halogen atom), C _{6 -.. 10} arylcarbonyl an amino group (the arylcarbonyl group is a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or a nitro group may be substituted.), C _{6 - 10} aryl-carbonyl (N-C1-4 alkyl Amino group (The arylcarbonyl (N-alkyl) amino Is a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or a nitro group may be substituted), benzyl carbonyl group, a formyl group, a carbamoyl group, C _{1 -. 4} alkylsulfonyl group, C _{6 -10} aryl sulfonyl group (wherein the alkylsulfonyl group and arylsulfonyl group, a halogen atom, C _{1 - 4} alkyl, C _{1 -. 4} group may be substituted alkoxy group, a cyano group or a nitro group), a sulfamoyl group, C _{1 - 4} alkyl sulfonamide group, a C _{6 -10} aryl sulfonamide group (said alkyl sulfonamide group and aryl sulfonamide group, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or a nitro group may be substituted), a bead (alkyl C _1-4 sulfone) imide group (the beads (alkyl sulfone) alkyl sulfone of the imide group is a halogen atom, C _{1 -. 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or may be substituted with a nitro group.), beads (C _6-10 aryl sulfone) imide group (the beads ( Reel sulfone) already aryl sulfone of deugi is a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or groups may be substituted by nitro), [N, N '- . (C 1 - 4 alkyl sulfone) (C _{6 - 10} aryl sulfone) already deugi (a [N, N '- (alkyl sulfone) (aryl sulfone) already in deugi alkyl sulfone and aryl alcohol phone, a halogen atom, C _{1 - 4} alkyl group, C _{1 - 4} alkoxy group, a cyano group or represents a nitro group may also be substituted). ₆ is an alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) _- (10) of the R ⁹ and R ¹⁰ are, each independently represent a hydrogen atom, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _1. or may be by a hydroxy group optionally substituted), C _{6 -14} aryl group (the aryl group, a halogen atom, a hydroxy group, a nitro group, a cyano group, C _{1 -6} alkyl group (said alkyl group, a halogen atom, a C _{1 - 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) or by a hydroxy group optionally may be substituted) or C _{1 -.. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) optionally substituted by May be substituted.) (11) and (12) of the R ⁹ and R ¹⁰ are, each independently represent a hydrogen atom, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 -6} optionally substituted alkoxy group (the alkoxy group is a halogen atom may be.), or by a hydroxy group optionally may be substituted.) or a C _{6 -14} aryl group (the aryl group, a halogen atom, a hydroxy group, a nitro group, a cyano group, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 -. 6} alkoxy group (said alkoxy group may be substituted by halogen atoms optionally), or may be by a hydroxy group optionally substituted) or C _{1 -6} alkoxy group (said alkoxy group may be substituted with a halogen atom, optionally May be optionally substituted). The partial ring structure A in formulas (11) and (12) is a 5, 6 or 7 membered ring which forms a condensed ring with the benzene ring moiety (both R ¹¹ (R ¹¹ is a halogen atom, a hydroxy group, a C _{1 -6} alkyl group (said alkyl group, a halogen atom, a hydroxy group, a cyano group, an amino group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, or C _{1 -4} alkoxycarbonyl group (the alkoxy group, the alkylcarbonyloxy may be substituted with a halogen atom group, alkylcarbonyl group and an alkoxycarbonyl group.) may also optionally be substituted.), C _{1 -6} alkoxycarbonyl group (the alkoxy group, a halogen atom, a hydroxy group, a cyano group, an amino group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkyl-carbonyl group, or C _{1 -4} alkoxycarbonyl group (the alkoxy group, the alkyl Carbonyloxy group, alkylcarbonylamino group and alkoxycarbonyl group may be optionally substituted with a halogen atom).), Nitro group, cyano group, formyl group, formamide group, carbamoyl group, sulfo group , a sulfonyl group, a sulfamoyl group, a sulfonyl group, amino group, carboxyl group, C _{1 - 6} alkylamino group, a di-C _{1 - 6} alkylamino group, C _{1 - 6} alkylcarbonyl group, C _{1 - 6} alkyl sulfonamide group, C _{6 - 14} aryl sulfonamide group, C _{1 - 6} alkylaminocarbonyl group, di C _{1 - 6} alkylaminocarbonyl group, C _{1 - 6} alkylcarbonyl group, C _{1 -6} alkoxycarbonyl groups, C _{1 - 6} alkylsulfonyl, C _{6 -14} arylsulfonyl group, or C _{6 -14} aryl group (the alkylamino group, a dialkylamino group, an alkyl carbonyl group, an alkyl sulfonamide group, a aryl sulfonamide group, an alkylamino group, a dialkylamino group, an alkyl car Beam group, alkoxycarbonyl group, alkylsulfonyl group, arylsulfonyl group and the arylcarbonyl group are, and may be optionally substituted with a halogen atom.) H is an integer of 1 to 6, and when h is 2 to 6, R ₁₁ may be the same or different.), And an oxygen atom, a nitrogen atom, or a sulfur atom as a constituent atom of the ring. It may be included alone or in combination, the number of unsaturated bonds in the ring is 1, 2 or 3, including the unsaturated bonds of the condensed benzene ring, the carbon atoms constituting the ring is carbonyl or thiocarbo Denotes a partial structure, X in the formula (13), NR ²⁰ represents the (R ^20, means a hydrogen atom or a C _{1 -4} alkyl group), Y in Formula (13) represents a bond, SO or SO ₂ , Expression (13) in Z is C _{1 -4} alkyl group (the alkyl group is from 1 to 5 halogen atoms or a phenyl group (the phenyl group, C _{1 -.} Be optionally substituted with may also optionally be substituted by ₄ alkyl group) is also Or a phenyl group (the phenyl group may be optionally substituted with a C _1-4 alkyl group.) ₆ alkoxy group (said alkoxy, _- formula (13) in W is a hydrogen atom, a hydroxy group, C ₁ May be optionally substituted with a halogen atom), halogen atom, C _{1 -. 4} alkyl or C _{1 - 6} alkyl sulfonamide group (wherein the alkyl group and alkyl sulfone amide group, represents a may be optionally substituted with a halogen atom). Expression (13) in the R ⁹ and R ¹⁰ are, each independently represent a hydrogen atom, C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 - 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom). Or optionally substituted by a hydroxyl group.) Or C _{6 -14} aryl group (the aryl group, a halogen atom, a hydroxy group, a nitro group, a cyano group, C _{1 - 6} alkyl group (said alkyl group, a halogen atom, a C _{1 - 6} alkoxy group (said alkoxy group is optionally substituted with a halogen atom there may be), or by a hydroxy group optionally may be substituted) or C _{1 -.} a ₆ alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom) may also optionally be substituted by a) it shows a)... Formula (14), formula (15), formula (16) or formula (17) characterized in that the chromium compound shown in the present invention is subjected to a subsidiary epoxidation. (Tue 5)

(Wherein R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , A, W, X, Y and Z are the same as above. The absolute arrangement of carbon atoms represented by * is (R) or ( A method for producing an optically active chromium oxide compound represented by S). The formula (1), formula (1 '), formula (2), formula (2'), formula (3), formula (3 '), formula (4) and formula (4') Using an optically active titanium complex represented by any one of formulas as a catalyst, The formula (10) in R ⁵ and R ⁶ are, each independently, a hydrogen atom, a cyano group, a nitro group, a halogen atom, a C _{1 -4} alkyl group (said alkyl group, a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, C _1-4 alkoxycarbonyl group (the alkoxy group, alkylcarbonyloxy group, alkylcarbonyl group and an alkoxycarbonyl group ., there may be arbitrarily substituted with halogen atom) it may also optionally be substituted with a), C _{1 -4} alkoxy group (the alkoxy group, a halogen atom, a hydroxy group, a cyano group, a nitro group, C _{1 - 4} alkoxy groups, C _{1 - 4} alkylcarbonyloxy group, C _{1 - 4} alkylcarbonyl group, C _1-4 alkoxycarbonyl group (the alkoxy group, alkylcarbonyloxy group, alkylcarbonyl group and an alkoxycarbonyl group, the halogen atom may be substituted with optionally Im a May be substituted.) To, C _{1 - 4} alkylcarbonyl group (the alkylcarbonyl amino group may be arbitrarily substituted with halogen atom), C _{1 - 4} alkyl-carbonyl (N-C _{1 -4} alkyl) amino group (wherein the alkyl-carbonyl (N - alkyl) amino group, and may be arbitrarily substituted with halogen atom), C _{6 -10} aryl-carbonyl (N-C _1-4 alkyl) amino group (the arylcarbonyl (N- alkyl) amino group, a halogen atom, C _{1 - 4} alkyl, C _{1 -. 4} alkoxy group, a cyano group or may be substituted with a nitro group), a carbamoyl group, a bead (C _1-4 alkyl sulfone) already deugi (the beads (alkyl sulfone) already in deugi alkyl sulfone is a halogen atom, C _{1 - 4} alkyl, C _{1 -. 4} alkoxy group, a cyano group or may be substituted by nitro), beads imide group (C _6-10 aryl sulfone) imide group (the beads (aryl sulfone) aryl sulfone, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a cyano group or a nitro group Substitution may be) or [N, N. '- ( C 1 - 4 alkyl sulfone) (C _{6 - 10} aryl sulfone) imide group (the [N, N' - (alkyl sulfone) (aryl sulfone) already alkyl sulfone and aryl sulfone of deugi is a halogen atom, C _{1 -. 4} alkyl, C _{1- 4} alkoxy group, a cyano group or may be substituted with a nitro group) represents, (10) of the R ⁷ is a hydrogen atom, a cyano group, a nitro group, a bead (C _{1 - 4} alkyl sulfone) already alkyl sulfone of deugi already deugi (the beads (alkyl sulfone) is a halogen atom, C _{1 - 4} alkyl groups, C _{1 -4} may be substituted with an alkoxy group, a cyano group or a nitro group.), beads _(-10 C ₆ aryl sulfone) imide group (the beads (aryl sulfone) is an aryl sulfone of the imide group, halogen atom, C _{1 - 4} alkyl, C _{1 -4} may be substituted with an alkoxy group, a cyano group or a nitro group), or [N, N '-. ( C 1 - 4 alkyl sulfone) (C _{6 - 10} aryl sulfone) imide group (the [N, N '- (alkyl sulfone) (aryl sulfone) already alkyl sulfone and aryl sulfone of deugi is a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} may be a substituted alkoxy group, a cyano group group or nitro .) Formula (10) in R ⁸ is a hydrogen atom, a nitro group or a C _{1 - 4} alkyl (The alkyl group may be optionally substituted with a halogen atom.), (10) of the R ⁹ and R ¹⁰ is, C _{1 - 6} alkyl (The alkyl group may be optionally substituted with a halogen atom.) A method for producing an optically active chromium oxide compound, wherein the chromium compound represented by the above formula (10) is epoxidized by a solvent and an oxidant. The R ⁵ and R ⁶ in the formula (10) are each independently a hydrogen atom, a nitro group, a fluorine atom, a methoxy group, a methylcarbonylamino group or a methylcarbonyl (N-ethyl) amino group. and, equation (10) it is of R ^7, a hydrogen atom, a nitro group or beads (C _{1 -4} alkyl sulfone) imide] is a group, (10) R ⁸ is a hydrogen atom, a nitro group or a trifluoromethyl group in the It is a romethyl group, R <^9> and R <^10> in Formula (10) represents a methyl group, The manufacturing method of the optically active chromium oxide compound characterized by the above-mentioned. The formula (1), formula (1 '), formula (2), formula (2'), formula (3), formula (3 '), formula (4) and formula (4') The partially active ring structure of A in Formula (11) or Formula (12) is used as the catalyst and the optically active titanium complex represented by any of the formulas (a), (b), (c) and (d) , Formula (e), formula (f), formula (g), formula (h), formula (i), formula (j), formula (k), formula (l), formula (m), formula (n) , Formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (ｖ), formula (w), formula (x) , Formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae), formula (af), formula (ag) and formula (ah) Is represented by either (Tue 6)

(Formula (a), formula (b), formula (e), formula (f), formula (g), formula (h), formula (i), formula (j), formula (k), formula (l) ), Formula (m), formula (n), formula (p), formula (q), formula (ｖ), formula (w), formula (x), formula (ab), formula (ae), formula (af ) and formula (ag) R ¹² and R ¹³ are, each independently, a hydrogen atom, C _{1 -6} alkyl group (the alkyl group of the halogen atom, C _{1 - 6} is an alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom .), an amino group, a hydroxy group, C _{6 - 14} aryl group, an aryl group with C _{2 -9} hetel (said aryl and heteroaryl groups all q of R ¹⁸ (R ¹⁸ represents the same meaning as R ^11, q is 1, for 2-3 represent an integer, q is 2 or 3, R ¹⁸ may be the same or different) may also optionally be substituted with a), C _{1 -. 6} alkylaminocarbonyl group, di C _{1 - 6} alkylamino a carbonyl group, C _{1 - 6} alkylcarbonyloxy group, C _{1 -6} alkylcarbonyl group (the alkylcarbonyloxy group and the alkylcarbonyl group is a halogen atom May also optionally be substituted with a), C _{1 -. 6} alkyl-carbonyl group, C _{3 -8} cycloalkyl group, a C _{1 - 6} alkoxycarbonyl, C _{1 -6} alkyl sulfonyl group (said cycloalkyl group, an alkoxycarbonyl group and an alkyl sulfonyl group may be arbitrarily substituted with halogen atom), a carboxyl group, C _{6 -. 14} aryl group (the aryl group may be arbitrarily substituted with halogen atom). Or C _{2 -9} may be optionally substituted with a heteroaryl group), C _{6 -. 14} aryl, C _2-9 heteroaryl group (wherein the aryl and heteroaryl groups all q of R ¹⁸ (R ¹⁸ is R ¹¹ . represents the same meanings, q is an integer of 1-3, in the case of q is 2 or 3, the R ¹⁸ may be the same or different) may also optionally be substituted with a), C _{1 -. 6} alkyl amino carbonyl group, a di-C _{1-amino -6} alkyl group, C _{1 - 6} alkylcarbonyl group, C _{3 - 8} cycloalkyl group, C _{1 - 6} alkoxycarbonyl group, C _{1 - 6} alkylsulfonyl, C _{6 - 14} arylsulfonyl group , C _{2 -9} heteroaryl sulfonyl group (the aryl sulfonyl and heteroaryl-sulfonyl group all q of R ¹⁸ (R ¹⁸ represents the same meaning as R ^11, q is an integer of 1 ~ 3, q is 2 or 3. in the case of, R ¹⁸ may be the same or different.) may also optionally be substituted with a), Reubok group, C _{6 -14} aryl group or a C _{2 -9} heteroaryl group (the aryl group and heteroaryl group are all q of R ¹⁸ (R ¹⁸ represents the same meaning as R ^11, q is an integer from 1 to 3 When q is 2 or 3, R ¹⁸ may be the same or different), and may be optionally substituted by Formula (a), Formula (b), Formula (c), Formula (d), Formula (f), Formula (g), Formula (h), Formula (j), Formula (k), Formula (m) , Formula (n), formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (ｖ), formula (w) formula (y), formula (z), formula (aa), formula (ab), formula (ac), R14, R15, R ¹⁶ and R ¹⁷ in the formula (ad), formula (ae) and formula (af) are each independently a hydrogen atom, a halogen atom, a C _{1 -6} alkyl group (said alkyl group, a halogen atom, C _{1 -. 6} is an alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), amino group, hydroxy group, C _{6 - 14} aryl group, C _{2 -. 9} heteroaryl group (wherein the aryl and heteroaryl groups all r of r ¹⁹ (r ¹⁹ represents the same meaning as r ^11, r represents a q and the same aesthetic) optionally by may be substituted), C _{1 -6} alkylamino group, a di C _{1- 6} alkylamino group, C _{1 -. 6} alkylcarbonyloxy group, C _{1 -6} alkylcarbonyl group (the alkylcarbonyloxy group and an alkyl carbonate Bonil May be optionally substituted with a halogen atom), C _{1 -6} alkylcarbonyl group, C _{3 -. 8} cycloalkyl group, a C _{1 - 6} alkoxycarbonyl, C _{1 -6} alkyl sulfonyl group (said cycloalkyl group, an alkoxycarbonyl group and the alkylsulfonyl group may be arbitrarily substituted with halogen atom), a carboxyl group, C _{6 -14} aryl group (the aryl group may be arbitrarily substituted with halogen atom) or a C _{2 -.. 9} heteroaryl group optionally may be substituted by there), C _{3 - 8} cycloalkyl group (said cycloalkyl group is a halogen atom, C _{1 - 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), May also optionally be substituted with amino group or hydroxy group), C _{1 -6} alkoxy group (said alkoxy group, a halogen atom, C _{1 -. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), a carboxyl group, an amino group, a hydroxy group, C _{6 - 14} aryl group or C _{2 - 9} heteroaryl group (wherein the aryl and heteroaryl groups all r of r ¹⁹ (r ¹⁹ represents the same meaning as r ^11, r has the same meaning as q. .) may also optionally be substituted by a) may also optionally be substituted with a), C _{1 -6} alkoxy group (said alkoxy group, a halogen atom, C _{1 -. 6} alkoxy group (said alkoxy group is optionally substituted with a halogen atom may be), a carboxyl group, a hydroxy group, C _{6 -. 14} aryl group or C _{2 - 9} heteroaryl group (wherein the aryl and heteroaryl groups all r of r ¹⁹ (r ¹⁹ represents the same meaning as r ^11, r Q .. The same meanings) may also optionally be substituted by a) may also optionally be substituted by a) hydroxyl group, C _{6 -. 14} aryl group, C _{2 -9} heteroaryl group (wherein the aryl and heteroaryl groups all r of r ¹⁹ (. r ¹⁹ represents the same meaning as r ^11, r has the same meaning as q) may also optionally be substituted with a), C _{1 -. 6} alkylcarbonyloxy group, a nitro group, a cyano group, a formyl group, forms an amide group, an amino group, a sulfo, C _{1 - 6} alkylamino group, a di-C _{1 - 6} alkylamino group, C _{6 - 14} aryl group, a C _{2 -9} heteroaryl group (the aryl group and heteroaryl amino group are all r of r ¹⁹ (. r ¹⁹ represents the same meaning as r ^11, r has the same meaning as q) may also optionally be substituted with a), C _{1 -. 6} alkylcarbonyl group, C _{1 - 6} alkyl sulfonamide group, a carbamoyl group, C _{1 - 6} Al Kill amino group, a di-C _{1 - 6} alkylaminocarbonyl group, C _{1 - 6} alkylcarbonyl group, C _{6 - 14} aryl group, a C _{2 -9} heteroaryl group (all of said aryl group and heteroaryl group have two r R ¹⁹ (R ¹⁹ represents the same meaning as R ^11, r has the same meaning as q) may also optionally be substituted with a), C _{1 -. 6} alkoxycarbonyl group, a sulfamoyl group, C _{1 - 6} alkylsulfonyl, C _{6 - 14} arylsulfonyl group, C _2-9 heteroaryl sulfonyl group (the aryl sulfonyl and heteroaryl-sulfonyl group of all r r ¹⁹ (r ¹⁹ represents the same meaning as r ^11, q and r are as defined are shown) may also optionally be substituted with a) carboxyl group or a C _{2 -9} heterocyclic methacrylic group (wherein the heterocyclyl rilneun, a halogen atom, C _{1 -. 6} alkyl group (said alkyl group, a halogen atom, C _{1 - 6} alkoxy Group (the alkoxy group is . Gen may reactor optionally may be substituted), may be optionally substituted with amino group, carboxyl group or hydroxy group), C _{1 -. 6} alkoxy group (said alkoxy group may be arbitrarily substituted with halogen atom), C _{6 -. 14} aryl group , C _{2 - 9} heteroaryl group (wherein the aryl and heteroaryl groups all r of r ¹⁹ (r ¹⁹ represents the same meaning as r ^11, r may be optionally substituted with the same meaning as q). .), a hydroxy group, a nitro group, a cyano group, a formyl group, forms an amide group, an amino group, a C _{1 - 6} alkylamino group, a di-C _{1 - 6} alkylamino group, C _{1 - 6} alkylcarbonyl group, C _{1 - 6} alkyl sulfone an amide group, a carbamoyl group, C _{1 - 6} alkylaminocarbonyl group, di C _{1 - 6} alkylaminocarbonyl group, C _{1 - 6} alkylcarbonyl group, C _{1 - 6} alkoxycarbonyl group, a sulfamoyl group, C _{1 - 6} alkylsulfonyl group, a carboxyl group or a C _{6 - 14} May also optionally be substituted by a reel group) represented by, Q in said Formula (c), Formula (d), Formula (p), Formula (q), Formula (iii), Formula (w), Formula (ab), Formula (ac), and Formula (ad) is O (Oxygen atom), S (sulfur atom), SO (sulfinyl group) or SO ₂ (sulfonyl group).) The chromene compound represented by the formula (11) or formula (12) is an oxidant and an oxidant. A method for producing an optically active chromium oxide compound, characterized by epoxidation. The method for producing an optically active chromium oxide compound according to claim 4, wherein R ⁹ and R ¹⁰ in Formula (11) or Formula (12) are methyl groups. The method according to claim 4 or 5, wherein A in the formula (11) or formula (12) is represented by the following formula (a), formula (b), formula (i), formula (k), formula (o), Expression (p), Expression (s), Expression (ｖ), Expression (y), Expression (ae), Expression (ag) or Expression (ah) (Tue 7)

(In formula, R <^12> , R <^{13> ,} R <^14> , R <^15> and R <^16> are the same as the description of Claim 4. The manufacturing method of the optically active chromium oxide compound represented by. The method according to claim 6, wherein A in formula (11) or formula (12) is represented by the formula (a), formula (b), formula (i), formula (k), formula (o), formula (p), Formula (s), formula (y), formula (y), formula (ae), formula (ag) or formula (ah), and formula (a), formula (b), formula (i) and formula (k) R ¹² in formula (p), formula (e), formula (ae) and formula (ag) And R ¹³ is each independently a hydrogen atom, C _{1 -6} alkyl group (said alkyl group is a halogen atom, C _{1 -.} May be optionally ₆ alkoxy group (the alkoxy group is substituted with a halogen atom), amino group or a hydroxy-de-Hi group optionally And (a), (b), (k), (o), (p), (s), (f), (y) and formula (ae) optionally of R ^14, R ¹⁵ and R ¹⁶ are, each independently represent a hydrogen atom, a halogen atom or a C _{1 -6} alkyl group (said alkyl group, a halogen atom, a C ₁₆ alkoxy group (the alkoxy group is a halogen atom may be substituted), an amino group, a hydroxy group, C _{1- 6} alkylaminocarbonyl group, di -c _{1 -6} alkylaminocarbonyl group, C _{1 -. 6} alkylcarbonyloxy group, C _{1- 6} alkylcarbonyl group (the alkylcarbonyloxy group optionally and alkyl group may be arbitrarily substituted with halogen atom), C _{1 -. 6} alkyl-carbonyl group, C _{3 -8} when Claw-alkyl group or a C _{1 -. 6} alkoxy may be optionally substituted with a carbonyl group) represents a, Q is O (process for producing an optically active chromene oxide compound, characterized in that represents an oxygen atom). The method according to claim 7, wherein A in formula (11) or formula (12) is represented by formula (a), formula (b), formula (i), formula (k), formula (o), formula (p), Formula (s), formula (y), formula (y), formula (ae), formula (ag) or formula (ah), and formula (a), formula (b), formula (i) and formula (k) , R ¹² and R ¹³ in formula (p), formula (e), formula (ae) and formula (ag) are hydrogen atoms and methyl groups, and formulas (a), (b), (k) and ( o), R ¹⁴ , R ¹⁵ and R ¹⁶ in formula (p), formula (s), formula (i), formula (y) and formula (ae) are each independently a hydrogen atom, a halogen atom, or C _{1 -6} alkyl group (said alkyl group, a halogen atom, C1-6 alkoxy group (which may be arbitrarily substituted with halogen atoms to the alkoxy group), amino group, hydroxy group, C _{1 -. 6} alkylaminocarbonyl group, di C _{1 - 6} alkylamino a carbonyl group, C _{1 - 6} alkylcarbonyloxy group, C _{1 -6} alkyl group (said alkyl carbonyloxy group and the alkylcarbonyl group may be optionally substituted with a halogen atom.), C _{1 - 6} alkylcarbonyl group, C _{3 - 8} Claw-alkyl group or a C _{1 -. 6} alkoxy may be optionally substituted with a carbonyl group) represents a, Q is O (process for producing an optically active chromene oxide compound that indicates oxygen atom). The formula (1), formula (1 '), formula (2), formula (2'), formula (3), formula (3 '), formula (4) and formula (4') Using the optically active titanium complex represented by any of the formulas as a catalyst, the chromene compound represented by the formula (13) in which both R ⁹ and R ¹⁰ in the formula (13) represents a methyl group as a solvent, A method for producing an optically active chromium oxide compound, characterized in that the subsidiary epoxidation. The method for producing an optically active chromium oxide compound according to claim 9, wherein W in the formula (13) is a hydrogen atom, a hydroxy group, a methoxy group, a chlorine atom, a bromine atom, a methyl group, an ethyl group, or a methane sulfone amide group. According to claim 9 or claim 10, wherein the formula (13) and in the Y SO ₂ (sulfonyl group), Z a method for producing an optically active chromene oxide compound, characterized in that represents a C _{1- 4} alkyl group. 11. The method of claim 10, wherein the formula (13), and Y is a bond in, Z is C _{1 -} optically active wherein the alkyl group represents a _4-chromen method for manufacturing a compound oxide. The formula (1), formula (1 '), formula (2), formula (2'), formula (3), formula (3 '), formula (4) and formula (4') R ¹ is in, C _{6 -22} aryl group (the aryl group, C _{1 -4} alkyl group (said alkyl group, a halogen atom optionally may be substituted.) C _{1 -7} alkoxy group, or a benzyloxy group optionally may be substituted and, an optically active or optically inactive) to indicate, R ² is a hydrogen atom, a halogen atom, C _{1 -. 4} alkyl, C _{1 - 4} alkoxy groups, C _{6 - 12} aryloxy or C _{6 -18} aryl group Indicates, R ³ is C _{1 - 4} alkyl group, C _{6 - 18} aryl group, or the two R ³ is with the case of forming the ring, represents a divalent group of C _{3 -5,} R ⁴ are each independently a hydrogen atom, a halogen atom, C _{1 - 4} alkyl, C _{1 - 4} alkoxy group, a denotes a nitro group or a cyano group, M is, TiJ ¹ J ² (for TiJ ¹ J ^2, Ti is a titanium atom, J ¹ and J ² are, each independently, a halogen atom, C _{1 - 4} alkoxy represents a de or, J ¹ and J ² is It becomes one and represents an oxygen atom, or J <^1> and J <^2> become one, and it forms a ring, and the said Formula (5) which is a bivalent group (partial structure O-E-O in formula, O is an oxygen atom. In formula (1), it is represented by said formula (6) as O-E-O, In formula (1 '), it is represented by said formula (6') as O-E-O, In formula (2), it is O- It is represented by said formula (7) as E-O, is represented by said formula (7 ') as O-E-O in formula (2'), and is represented by said formula (8) as O-E-O in formula (3). Is represented by the formula (8 ') as O-E-O in formula (3'), is represented by the formula (9) as O-E-O in formula (4), and is represented by formula (4). Iv) is represented by the above formula (9 ') as O-E-O, b is an integer of 1 to 10, and R ¹ , R ² , R ³ And R ⁴ is as defined above.) A process for producing an optically active chromium oxide compound. The formula (1), formula (1 '), formula (2), formula (2'), formula (3), formula (3 '), formula (4) and formula (4'). R ¹ is in, a phenyl group (phenyl group it is, is C _1-4 alkyl group (said alkyl group may be arbitrarily substituted with halogen atom), a benzyloxy group, or a C _{1 -. 7} alkoxy group may be optionally substituted.) or It represents a naphthyl group (the naphthyl group, C _{1 -. - 4} alkyl group (said alkyl group, halogen atoms may be optionally substituted to), C _{1 7} alkoxycarbonyl group, or optionally may be substituted with phenyl.), R ² represents a hydrogen atom, R ³ represents a C _{3 -5} divalent group in which two R ³ are one to form a ring, R ⁴ represents a hydrogen atom, M is, TiJ ¹ J ² (for TiJ ¹ J ^2, Ti is a titanium atom, J ¹ and J ² are, each independently, a halogen atom, C _{1 -4} alkoxy, or DE, J ¹ and J ² It becomes one and represents an oxygen atom, or J <^1> and J <^2> become one, and it forms a ring, and the said Formula (5) which is a bivalent group (partial structure O-E-O in formula, O is an oxygen atom. In formula (1), it is represented by said formula (6) as O-E-O, In formula (1 '), it is represented by said formula (6') as O-E-O, In formula (2) It is represented by said formula (7) as E-O, is represented by said formula (7 ') as O-E-O in formula (2'), is represented by said formula (8 ') as HO-E-O, In formula (4), it is represented by said formula (9) as O-E-O, In formula (4 '), it is represented by said formula (9') as O-E-O, and b is an integer of 1-10. ^{, R 1, R 2, R} 3 and R ⁴ is optically active, characterized in that indicating the same as above) shows a.) The method of romen oxide compound. The use amount of the optically active titanium complex is 0.001 in any one of Claims 1-14 with respect to the chromium compound represented by Formula (10), Formula (11), Formula (12), or Formula (13). Method of producing an optically active chromium oxide compound, characterized in that ~ ~ 100 mol%. The solvent used in the subsidiary epoxidation reaction is a halogen solvent, an aromatic hydrocarbon solvent, an ester solvent, an ether solvent, a nitrile solvent, or an alcohol solvent. Or a mixture of the above solvents. The oxidizing agent used for a subsidiary epoxidation reaction is an iodine benzene, sodium hypochlorite, m-chloro perbenzoic acid, a foulone (Dupont.trademark), hydrogen peroxide, urea-. Optically active, characterized in that it is a hydrogen peroxide adduct (UHP), oxadiridine, N-methylmorpholine oxide (NMO), t-butylhydrofeloxide (TBHP), cumene hydrofeloxide (CHP) or a mixture of these oxidants Process for preparing chromium oxide compound. 18. The method for producing an optically active chromium oxide compound according to claim 17, wherein the oxidant used in the subtitle epoxidation reaction is hydrogen peroxide water, urea-hydrogen peroxide adduct (UHP), or a mixture of these oxidants. The method for producing an optically active chromium oxide compound according to claim 18, wherein the oxidizing agent used in the subsidiary epoxidation reaction is hydrogen peroxide and has a concentration of 1 to 100 mass%. The chromium of any one of Claims 1-14 whose usage-amount of the oxidizing agent used for a subsidiary epoxidation reaction is represented by said Formula (10), Formula (11), Formula (12), or Formula (13). It is 1-10 equivalent with respect to a compound, The manufacturing method of the optically active chromium oxide compound characterized by the above-mentioned. The method for producing an optically active chromium oxide compound according to claim 20, wherein the method of adding the oxidizing agent used in the subsidiary epoxidation reaction is divided addition or continuous addition. 22. The method for producing an optically active chromium oxide compound according to claim 21, wherein the method of adding the oxidant used in the subsidiary epoxidation reaction is continuous addition, and the addition rate thereof is 0.01 to 40000 equivalents every hour. The method for producing an optically active chromium oxide compound according to claim 21, wherein the addition method of the oxidizing agent used for the subsidiary epoxidation reaction is divided addition and the number of division is in the range of 2 to 100. The method for producing an optically active chromium oxide compound according to any one of claims 1 to 23, wherein the reaction temperature of the subsidiary epoxidation reaction is from 0 ° C to the reflux temperature of the solvent used. The method for producing an optically active chromium oxide compound according to any one of claims 1 to 24, wherein the pressure range in the reaction system of the subsidiary epoxidation reaction is 10 kPa to 1100 kPa.